Advanced search
Publication Cover
Drug Metabolism Reviews Volume 41, 2009 - Issue 2
Submit an article Journal homepage
16,466
Views
580
CrossRef citations to date
0
Altmetric
Review Article

Polymorphism of human cytochrome P450 enzymes and its clinical impact

Shu-Feng ZhouSchool of Health Sciences, RMIT University, Bundoora, Victoria, AustraliaCorrespondence[email protected]
,
Jun-Ping LiuDepartment of Immunology, Central and Eastern Clinical School, Monash University, Prahran, Victoria, Australia
&
Balram ChowbayLaboratory of Clinical Pharmacology, Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Center, Singapore
Pages 89-295 | Accepted 24 Feb 2009, Published online: 01 May 2009

References

  • Aapro, M. (2005). 5-HT(3)-receptor antagonists in the management of nausea and vomiting in cancer and cancer treatment. Oncology 69:97–109.
  • Aapro, M. Blower, P. (2005). 5-hydroxytryptamine type-3 receptor antagonists for chemotherapy-induced and radiotherapy-induced nausea and emesis: can we safely reduce the dose of administered agents? Cancer 104:1–18.
  • Abass, K., Reponen, P., Turpeinen, M., Jalonen, J. Pelkonen, O. (2007). Characterization of diuron N-demethylation by mammalian hepatic microsomes and cDNA-expressed human cytochrome P450 enzymes. Drug Metab Dispos 35:1634–1641.
  • Abdel-Rahman, S. M., Leeder, J. S., Wilson, J. T., Gaedigk, A., Gotschall, R. R., Medve, R., Liao, S., Spielberg, S. P., Kearns, G. L. (2002). Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation. J Clin Pharmacol 42:24–29.
  • Abelo, A., Andersson, T. B., Antonsson, M., Naudot, A. K., Skanberg, I. Weidolf, L. (2000). Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 28:966–972.
  • Abolfathi, Z., Fiset, C., Gilbert, M., Moerike, K., Belanger, P. M. Turgeon, J. (1993). Role of polymorphic debrisoquin 4-hydroxylase activity in the stereoselective disposition of mexiletine in humans. J Pharmacol Exp Ther 266:1196–1201.
  • Adams, S. S., Bresloff, P. Mason, C. G. (1976). Pharmacological differences between the optical isomers of ibuprofen: evidence for metabolic inversion of the (-)-isomer. J Pharm Pharmacol 28:256–257.
  • Adedoyin, A., Prakash, C., O’Shea, D., Blair, I. A. Wilkinson, G. R. (1994). Stereoselective disposition of hexobarbital and its metabolites: relationship to the S-mephenytoin polymorphism in Caucasian and Chinese subjects. Pharmacogenetics 4:27–38.
  • Adkins, J. C. Noble, S. (1998). Efavirenz. Drugs 56: 1055–1064; discussion, 1065–1056.
  • Agudo, A., Sala, N., Pera, G., Capella, G., Berenguer, A., Garcia, N., et al. (2006). Polymorphisms in metabolic genes related to tobacco smoke and the risk of gastric cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev 15:2427–2434.
  • Agundez, J. A., Ledesma, M. C., Ladero, J. M. Benitez, J. (1995). Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population. Ther Clin Pharmacol 57:265–269.
  • Agundez, J. A., Ramirez, R., Hernandez, M., Llerena, A. Benitez, J. (1997). Molecular heterogeneity at the CYP2D gene locus in Nicaraguans: impact of gene-flow from Europe. Pharmacogenetics 7:337–340.
  • Aitchison, K. J., Jann, M. W., Zhao, J. H., Sakai, T., Zaher, H., Wolff, K., Collier, D. A., Kerwin, R. W. Gonzalez, F. J. (2000). Clozapine pharmacokinetics and pharmacodynamics studied with Cyp1A2-null mice. J Psychopharmacol 14:353–359.
  • Aithal, G. P., Day, C. P., Leathart, J. B. Daly, A. K. (2000). Relationship of polymorphism in CYP2C9 to genetic susceptibility to diclofenac-induced hepatitis. Pharmacogenetics 10:511–518.
  • Ajroud-Driss, S., Saeed, M., Khan, H., Siddique, N., Hung, W. Y., Sufit, R., Heller, S., Armstrong, J., Casey, P., Siddique, T. Lukas, T. J. (2007). Riluzole metabolism and CYP1A1/2 polymorphisms in patients with ALS. Amyotroph Lateral Scler 8:305–309.
  • Aklillu, E., Carrillo, J. A., Makonnen, E., Hellman, K., Pitarque, M., Bertilsson, L. Ingelman-Sundberg, M. (2003). Genetic polymorphism of CYP1A2 in Ethiopians affecting induction and expression: characterization of novel haplotypes with single-nucleotide polymorphisms in intron 1. Mol Pharmacol 64:659–669.
  • Aklillu, E., Kalow, W., Endrenyi, L., Harper, P., Miura, J. Ozdemir, V. (2007). CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics 17:989–993.
  • Aklillu, E., Persson, I., Bertilsson, L., Johansson, I., Rodrigues, F. Ingelman-Sundberg, M. (1996). Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J Pharmacol Exp Ther 278:441–446.
  • Aktas, D., Guney, I., Alikasifoglu, M., Yuce, K., Tuncbilek, E. Ayhan, A. (2002). CYP1A1 gene polymorphism and risk of epithelial ovarian neoplasm. Gynecol Oncol 86:124–128.
  • Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T. Chiba, K. (2007). Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metab Dispos 35:72–78.
  • Al Koudsi, N., Mwenifumbo, J. C., Sellers, E. M., Benowitz, N. L., Swan, G. E. Tyndale, R. F. (2006). Characterization of the novel CYP2A6*21 allele using in vivo nicotine kinetics. Eur J Clin Pharmacol 62:481–484.
  • Albrecht, W., Unger, A., Nussler, A. K. Laufer, S. (2008). In vitro metabolism of 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2, 3-dihydro-1H-pyrrolizin-5-yl] acetic acid (licofelone, ML3000), an inhibitor of cyclooxygenase-1 and -2 and 5-lipoxygenase. Drug Metab Dispos 36:894–903.
  • Albus, M., Botschev, C., Muller-Spahn, F., Naber, D., Munch, U. Ackenheil, M. (1986). Clinical and biochemical effects of nicergoline in chronic schizophrenic patients. Pharmacopsychiatry 19:101–105.
  • Alexanderson, B., Evans, D. A. Sjoqvist, F. (1969). Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy. Br Med J 4:764–768.
  • Alkalay, D., Wagner, W. E., Jr., Carlsen, S., Khemani, L., Volk, J., Bartlett, M. F. LeSher, A. (1980). Bioavailability and kinetics of maprotiline. Clin Pharmacol Ther 27:697–703.
  • Allabi, A. C., Gala, J. L. Horsmans, Y. (2005). CYP2C9, CYP2C19, ABCB1 (MDR1) genetic polymorphisms and phenytoin metabolism in a black Beninese population. Pharmacogenet Genomics 15:779–786.
  • Allabi, A. C., Gala, J. L., Horsmans, Y., Babaoglu, M. O., Bozkurt, A., Heusterspreute, M. Yasar, U. (2004). Functional impact of CYP2C9*5, CYP2C9*6, CYP2C9*8, and CYP2C9*11 in vivo among black Africans. Clin Pharmacol Ther 76:113–118.
  • Allorge, D., Chevalier, D., Lo-Guidice, J. M., Cauffiez, C., Suard, F., Baumann, P., Eap, C. B. Broly, F. (2003). Identification of a novel splice-site mutation in the CYP1A2 gene. Br J Clin Pharmacol 56:341–344.
  • Anderson, J. L., Stewart, J. R., Perry, B. A., Van Hamersveld, D. D., Johnson, T. A., Conard, G. J., Chang, S. F., Kvam, D. C. Pitt, B. (1981). Oral flecainide acetate for the treatment of ventricular arrhythmias. N Engl J Med 305:473–477.
  • Andersson, T., Holmberg, J., Rohss, K. Walan, A. (1998). Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole. Br J Clin Pharmacol 45:369–375.
  • Andersson, T., Miners, J. O., Veronese, M. E. Birkett, D. J. (1994). Identification of human liver cytochrome P450 isoforms mediating secondary omeprazole metabolism. Br J Clin Pharmacol 37:597–604.
  • Andersson, T. Weidolf, L. (2008). Stereoselective disposition of proton pump inhibitors. Clin Drug Investig 28:263–279.
  • Anggard, E., Gunne, L. M., Homstrand, J., McMahon, R. E., Sandberg, C. G. Sullivan, H. R. (1975). Disposition of methadone in methadone maintenance. Clin Pharmacol Ther 17:258–266.
  • Angiolillo, D. J., Bates, E. R. Bass, T. A. (2008). Clinical profile of prasugrel, a novel thienopyridine. Am Heart J 156:S16–S22.
  • Antonaccio, M. J., Gomoll, A. W. Byrne, J. E. (1989). Encainide. Cardiovasc Drugs Ther 3:691–710.
  • Anttila, S. A. Leinonen, E. V. (2001). A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 7:249–264.
  • Anzenbacherova, E., Anzenbacher, P., Perlik, F. Kvetina, J. (2000). Use of a propafenone metabolic ratio as a measure of CYP2D6 activity. Int J Clin Pharmacol Ther 38:426–429.
  • Aoyama, T., Yamano, S., Waxman, D. J., Lapenson, D. P., Meyer, U. A., Fischer, V., Tyndale, R., Inaba, T., Kalow, W., Gelboin, H. V. et al. (1989). Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J Biol Chem 264:10388–10395.
  • Apak, T. I. Duffel, M. W. (2004). Interactions of the stereoisomers of alpha-hydroxytamoxifen with human hydroxysteroid sulfotransferase SULT2A1 and rat hydroxysteroid sulfotransferase STa. Drug Metab Dispos 32:1501–1508.
  • Aplenc, R., Glatfelter, W., Han, P., Rappaport, E., La, M., Cnaan, A., Blackwood, M. A., Lange, B. Rebbeck, T. (2003). CYP3A genotypes and treatment response in paediatric acute lymphoblastic leukaemia. Br J Haematol 122:240–244.
  • Arcamone, F., Glasser, A. G., Grafnetterova, J., Minghetti, A. Nicolella, V. (1972). Studies on the metabolism of ergoline derivatives. Metabolism of nicergoline in man and in animals. Biochem Pharmacol 21:2205–2213.
  • Ariyoshi, N., Miyazaki, M., Toide, K., Sawamura, Y. Kamataki, T. (2001a). A single-nucleotide polymorphism of CYP2b6 found in Japanese enhances catalytic activity by autoactivation. Biochem Biophys Res Commun 281:1256–1260.
  • Ariyoshi, N., Oguri, K., Koga, N., Yoshimura, H. Funae, Y. (1995). Metabolism of highly persistent PCB congener, 2,4,5,2’,4’,5’-hexachlorobiphenyl, by human CYP2B6. Biochem Biophys Res Commun 212:455–460.
  • Ariyoshi, N., Sawamura, Y. Kamataki, T. (2001b). A novel single nucleotide polymorphism altering stability and activity of CYP2a6. Biochem Biophys Res Commun 281:810–814.
  • Ariyoshi, N., Sekine, H., Nakayama, K., Saito, K., Miyamoto, A. Kamataki, T. (2004). Identification of deletion-junction site of CYP2A6*4B allele lacking entire coding region of CYP2A6 in Japanese. Pharmacogenetics 14:701–705.
  • Ariyoshi, N., Sekine, H., Saito, K. Kamataki, T. (2002). Characterization of a genotype previously designated as CYP2A6 D-type: CYP2A6*4B, another entire gene deletion allele of the CYP2A6 gene in Japanese. Pharmacogenetics 12:501–504.
  • Ariyoshi, N., Takahashi, Y., Miyamoto, M., Umetsu, Y., Daigo, S., Tateishi, T., Kobayashi, S., Mizorogi, Y., Loriot, M. A., Stucker, I., Beaune, P., Kinoshita, M. Kamataki, T. (2000). Structural characterization of a new variant of the CYP2A6 gene (CYP2A6*1B) apparently diagnosed as heterozygotes of CYP2A6*1A and CYP2A6*4C. Pharmacogenetics 10:687–693.
  • Arpino, G., Nair Krishnan, M., Doval Dinesh, C., Bardou, V. J., Clark, G. M. Elledge, R. M. (2003). Idoxifene versus tamoxifen: a randomized comparison in postmenopausal patients with metastatic breast cancer. Ann Oncol 14:233–241.
  • Arroyo, E., Valenzuela, B., Portilla, J., Climent-Grana, E., Perez-Ruixo, J. J. Merino, E. (2007). Pharmacokinetics of methadone in human-immunodeficiency-virus–infected patients receiving nevirapine once-daily. Eur J Clin Pharmacol 63:669–675.
  • Atkinson, A., Singleton, A. B., Steward, A., Ince, P. G., Perry, R. H., McKeith, I. G., Fairbairn, A. F., Edwardson, J. A., Daly, A. K. Morris, C. M. (1999). CYP2D6 is associated with Parkinson’s disease but not with dementia with Lewy Bodies or Alzheimer’s disease. Pharmacogenetics 9:31–35.
  • Aynacioglu, A. S., Brockmoller, J., Bauer, S., Sachse, C., Guzelbey, P., Ongen, Z., Nacak, M. Roots, I. (1999). Frequency of cytochrome P450 CYP2C9 variants in a Turkish population and functional relevance for phenytoin. Br J Clin Pharmacol 48:409–415.
  • Azuma, J. Nonen, S. (2009). Chronic heart failure: beta-blockers and pharmacogenetics. Eur J Clin Pharmacol 65:3–17.
  • Bachus, R., Bickel, U., Thomsen, T., Roots, I. Kewitz, H. (1999). The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6. Pharmacogenetics 9:661–668.
  • Back, D., Gibbons, S. Khoo, S. (2003). Pharmacokinetic drug interactions with nevirapine. J Acquir Immune Defic Syndr 34 (Suppl 1):S8–S14.
  • Backman, J. T., Kyrklund, C., Neuvonen, M. Neuvonen, P. J. (2002). Gemfibrozil greatly increases plasma concentrations of cerivastatin. Clin Pharmacol Ther 72:685–691.
  • Bae, S. K., Cao, S., Seo, K. A., Kim, H., Kim, M. J., Shon, J. H., Liu, K. H., Zhou, H. H. Shin, J. G. (2008). Cytochrome P450 2B6 (CYP2B6) catalyzes the formation of pharmacologically active sibutramine metabolites in human liver microsomes. Drug Metab Dispos 36:1679–1688.
  • Baede-van Dijk, P. A., Hugen, P. W., Verweij-van Wissen, C. P., Koopmans, P. P., Burger, D. M. Hekster, Y. A. (2001). Analysis of variation in plasma concentrations of nelfinavir and its active metabolite M8 in HIV-positive patients. Aids 15:991–998.
  • Bagshaw, S. M., Delaney, A., Haase, M., Ghali, W. A. Bellomo, R. (2007). Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. Crit Care Resusc 9:60–68.
  • Bahadur, N., Leathart, J. B., Mutch, E., Steimel-Crespi, D., Dunn, S. A., Gilissen, R., Houdt, J. V., Hendrickx, J., Mannens, G., Bohets, H., Williams, F. M., Armstrong, M., Crespi, C. L. Daly, A. K. (2002). CYP2C8 polymorphisms in Caucasians and their relationship with paclitaxel 6alpha-hydroxylase activity in human liver microsomes. Biochem Pharmacol 64:1579–1589.
  • Baiocchi, L., Frigerio, A., Giannangeli, M. Palazzo, G. (1974). Basic metabolites of trazodone in humans. Arzneimittelforschung 24:1699–1706.
  • Baird-Lambert, J., Doyle, P. E., Thomas, D., Jager-Roman, E., Cvejic, M. Buchanan, N. (1984). Theophylline metabolism in preterm neonates during the first weeks of life. Dev Pharmacol Ther 7:239–244.
  • Bajpai, M., Roskos, L. K., Shen, D. D. Levy, R. H. (1996). Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolite. Drug Metab Dispos 24:1401–1403.
  • Baldwin, S. J., Clarke, S. E. Chenery, R. J. (1999). Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of rosiglitazone. Br J Clin Pharmacol 48:424–432.
  • Ball, S. E., Forrester, L. M., Wolf, C. R. Back, D. J. (1990). Differences in the cytochrome P-450 isoenzymes involved in the 2-hydroxylation of oestradiol and 17 alpha-ethinyloestradiol. Relative activities of rat and human liver enzymes. Biochem J 267:221–226.
  • Ball, S. E., Scatina, J., Kao, J., Ferron, G. M., Fruncillo, R., Mayer, P., Weinryb, I., Guida, M., Hopkins, P. J., Warner, N. Hall, J. (1999). Population distribution and effects on drug metabolism of a genetic variant in the 5’ promoter region of CYP3A4. Clin Pharmacol Ther 66:288–294.
  • Banerji, A., Long, A. A. Camargo, C. A.Jr., (2007). Diphenhydramine versus nonsedating antihistamines for acute allergic reactions: a literature review. Allergy Asthma Proc 28:418–426.
  • Bao, Z., He, X. Y., Ding, X., Prabhu, S. Hong, J. Y. (2005). Metabolism of nicotine and cotinine by human cytochrome P450 2A13. Drug Metab Dispos 33:258–261.
  • Barbey, J. T., Thompson, K. A., Echt, D. S., Woosley, R. L. Roden, D. M. (1988). Antiarrhythmic activity, electrocardiographic effects and pharmacokinetics of the encainide metabolites O-desmethyl encainide and 3-methoxy-O-desmethyl encainide in man. Circulation 77:380–391.
  • Barbosa-Sicard, E., Markovic, M., Honeck, H., Christ, B., Muller, D. N. Schunck, W. H. (2005). Eicosapentaenoic acid metabolism by cytochrome P450 enzymes of the CYP2C subfamily. Biochem Biophys Res Commun 329:1275–1281.
  • Bardou, M. Martin, J. (2008). Pantoprazole: from drug metabolism to clinical relevance. Expert Opin Drug Metab Toxicol 4:471–483.
  • Bardy, A. H., Seppala, T., Salokorpi, T., Granstrom, M. L. Santavuori, P. (1991). Monitoring of concentrations of clobazam and norclobazam in serum and saliva of children with epilepsy. Brain Dev 13:174–179.
  • Bargetzi, M. J., Aoyama, T., Gonzalez, F. J. Meyer, U. A. (1989). Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4. Clin Pharmacol Ther 46:521–527.
  • Barham, H. M., Lennard, M. S. Tucker, G. T. (1994). An evaluation of cytochrome P450 isoform activities in the female dark agouti (DA) rat: relevance to its use as a model of the CYP2D6 poor metaboliser phenotype. Biochem Pharmacol 47:1295–1307.
  • Barner, E. L. Gray, S. L. (1998). Donepezil use in Alzheimer’s disease. Ann Pharmacother 32:70–77.
  • Barnes, P. J. (2005). Theophylline in chronic obstructive pulmonary disease: new horizons. Proc Am Thorac Soc 2:334–339; discussion, 340–331.
  • Barrenetxe, J., Delagrange, P. Martinez, J. A. (2004). Physiological and metabolic functions of melatonin. J Physiol Biochem 60:61–72.
  • Barry, M., Mulcahy, F., Merry, C., Gibbons, S. Back, D. (1999). Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection. Clin Pharmacokinet 36:289–304.
  • Barsoum, N. J., Gough, A. W., Sturgess, J. M. de la Iglesia, F. A. (1986). Parkinson-like syndrome in nonhuman primates receiving a tetrahydropyridine derivative. Neurotoxicology 7:119–126.
  • Baskys, A. Hou, A. C. (2007). Vascular dementia: pharmacological treatment approaches and perspectives. Clin Interv Aging 2:327–335.
  • Bates, D. J., Foster, A. B., Griggs, L. J., Jarman, M., Leclercq, G. Devleeshouwer, N. (1982). Metabolism of tamoxifen by isolated rat hepatocytes: anti-estrogenic activity of tamoxifen N-oxide. Biochem Pharmacol 31:2823–2827.
  • Baughman, T. M., Graham, R. A., Wells-Knecht, K., Silver, I. S., Tyler, L. O., Wells-Knecht, M. Zhao, Z. (2005). Metabolic activation of pioglitazone identified from rat and human liver microsomes and freshly isolated hepatocytes. Drug Metab Dispos 33:733–738.
  • Baumann, P., Bosshart, P., Gabris, G., Gastpar, M., Koeb, L. Woggon, B. (1988). Acetylation of maprotiline and desmethylmaprotiline in depressive patients phenotyped with sulfamidine, debrisoquine, and mephenytoin. Arzneimittelforschung 38:292–296.
  • Beckett, A. H. Chidomere, E. C. (1977). The identification and analysis of mexiletine and its metabolic products in man. J Pharm Pharmacol 29:281–285.
  • Begg, E. J., Sharman, J. R., Kidd, J. E., Sainsbury, R. Clark, D. W. (1989). Variability in the elimination of mianserin in elderly patients. Br J Clin Pharmacol 27:445–451.
  • Begre, S., von Bardeleben, U., Ladewig, D., Jaquet-Rochat, S., Cosendai-Savary, L., Golay, K. P., Kosel, M., Baumann, P. Eap, C. B. (2002). Paroxetine increases steady-state concentrations of (R)-methadone in CYP2D6 extensive but not poor metabolizers. J Clin Psychopharmacol 22:211–215.
  • Belliard, A. M., Baune, B., Fakhfakh, M., Hocquemiller, R. Farinotti, R. (2003). Determination of the human cytochrome P450s involved in the metabolism of 2n-propylquinoline. Xenobiotica 33:341–355.
  • Belpaire, F. M., Wijnant, P., Temmerman, A., Rasmussen, B. B. Brosen, K. (1998). The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol 54:261–264.
  • Benitez, J., Barquero, M. S., Coria, F., Molina, J. A., Jimenez-Jimenez, F. J. Ladero, J. M. (1993). Oxidative polymorphism of debrisoquine is not related to the risk of Alzheimer’s disease. J Neurol Sci 117:8–11.
  • Benjamin, B. Burns, A. (2007). Donepezil for Alzheimer’s disease. Expert Rev Neurother 7:1243–1249.
  • Benowitz, N. L. (2008). Clinical pharmacology of nicotine: implications for understanding, preventing, and treating tobacco addiction. Clin Pharmacol Ther 83:531–541.
  • Benowitz, N. L., Jacob, P., 3rd, Perez-Stable, E. (1996). CYP2D6 phenotype and the metabolism of nicotine and cotinine. Pharmacogenetics 6:239–242.
  • Benowitz, N. L., Perez-Stable, E. J., Fong, I., Modin, G., Herrera, B. Jacob, P.3rd. (1999). Ethnic differences in N-glucuronidation of nicotine and cotinine. J Pharmacol Exp Ther 291:1196–1203.
  • Benowitz, N. L., Swan, G. E., Jacob, P., 3rd, Lessov-Schlaggar, C. N. Tyndale, R. F. (2006). CYP2A6 genotype and the metabolism and disposition kinetics of nicotine. Clin Pharmacol Ther 80:457–467.
  • Bensimon, G., Lacomblez, L., Delumeau, J. C., Bejuit, R., Truffinet, P. Meininger, V. (2002). A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis. J Neurol 249:609–615.
  • Bensimon, G., Lacomblez, L. Meininger, V. (1994). A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N Engl J Med 330:585–591.
  • Berecz, R., de la Rubia, A., Dorado, P., Fernandez-Salguero, P., Dahl, M. L. A, L. L. (2003). Thioridazine steady-state plasma concentrations are influenced by tobacco smoking and CYP2D6, but not by the CYP2C9 genotype. Eur J Clin Pharmacol 59:45–50.
  • Bergshoeff, A. S., Fraaij, P. L., Ndagijimana, J., Verweel, G., Hartwig, N. G., Niehues, T., De Groot, R., Burger, D. M. (2005). Increased dose of lopinavir/ritonavir compensates for efavirenz-induced drug-drug interaction in HIV-1-infected children. J Acquir Immune Defic Syndr 39:63–68.
  • Berkman, C. E., Park, S. B., Wrighton, S. A. Cashman, J. R. (1995). In vitro–in vivo correlations of human (S)-nicotine metabolism. Biochem Pharmacol 50:565–570.
  • Bernal, M. L., Sinues, B., Johansson, I., McLellan, R. A., Wennerholm, A., Dahl, M. L., Ingelman-Sundberg, M. Bertilsson, L. (1999). Ten percent of North Spanish individuals carry duplicated or triplicated CYP2D6 genes associated with ultrarapid metabolism of debrisoquine. Pharmacogenetics 9:657–660.
  • Bernauer, U., Heinrich-Hirsch, B., Tonnies, M., Peter-Matthias, W. Gundert-Remy, U. (2006). Characterisation of the xenobiotic-metabolizing cytochrome P450 expression pattern in human lung tissue by immunochemical and activity determination. Toxicol Lett 164:278–288.
  • Berthou, F., Dreano, Y., Belloc, C., Kangas, L., Gautier, J. C. Beaune, P. (1994). Involvement of cytochrome P450 3A enzyme family in the major metabolic pathways of toremifene in human liver microsomes. Biochem Pharmacol 47:1883–1895.
  • Bertilsson, L. (1995). Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin Pharmacokinet 29:192–209.
  • Bertilsson, L. (2007). Metabolism of antidepressant and neuroleptic drugs by cytochrome p450s: clinical and interethnic aspects. Clin Pharmacol Ther 82:606–609.
  • Bertilsson, L., Baillie, T. A. Reviriego, J. (1990). Factors influencing the metabolism of diazepam. Pharmacol Ther 45:85–91.
  • Bertilsson, L., Carrillo, J. A., Dahl, M. L., Llerena, A., Alm, C., Bondesson, U., Lindstrom, L., Rodriguez de la Rubia, I., Ramos, S. Benitez, J. (1994) Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br J Clin Pharmacol 38:471–473.
  • Bertilsson, L., Dahl, M. L., Sjoqvist, F., Aberg-Wistedt, A., Humble, M., Johansson, I., Lundqvist, E. Ingelman-Sundberg, M. (1993). Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine. Lancet 341:63.
  • Bertilsson, L., Henthorn, T. K., Sanz, E., Tybring, G., Sawe, J. Villen, T. (1989). Importance of genetic factors in the regulation of diazepam metabolism: relationship to S-mephenytoin, but not debrisoquin, hydroxylation phenotype. Clin Pharmacol Ther 45:348–355.
  • Bertilsson, L., Lou, Y. Q., Du, Y. L., Liu, Y., Kuang, T. Y., Liao, X. M., Wang, K. Y., Reviriego, J., Iselius, L. Sjoqvist, F. (1992). Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquin and S-mephenytoin. Clin Pharmacol Ther 51:388–397.
  • Bertrand, M. E., Rupprecht, H. J., Urban, P. Gershlick, A. H. (2000). Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting: the clopidogrel aspirin stent international cooperative study (CLASSICS). Circulation 102:624–629.
  • Beverage, J. N., Sissung, T. M., Sion, A. M., Danesi, R. Figg, W. D. (2007). CYP2D6 polymorphisms and the impact on tamoxifen therapy. J Pharm Sci 96:2224–2231.
  • Bhatt, D. L., Chew, D. P., Hirsch, A. T., Ringleb, P. A., Hacke, W. Topol, E. J. (2001). Superiority of clopidogrel versus aspirin in patients with prior cardiac surgery. Circulation 103:363–368.
  • Bidstrup, T. B., Bjornsdottir, I., Sidelmann, U. G., Thomsen, M. S. Hansen, K. T. (2003). CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol 56:305–314.
  • Bidstrup, T. B., Damkier, P., Olsen, A. K., Ekblom, M., Karlsson, A. Brosen, K. (2006). The impact of CYP2C8 polymorphism and grapefruit juice on the pharmacokinetics of repaglinide. Br J Clin Pharmacol 61:49–57.
  • Bijl, M. J., van Schaik, R. H., Lammers, L. A., Hofman, A., Vulto, A. G., van Gelder, T., Stricker, B. H. Visser, L. E. (2009a). The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users. Breast Cancer Res Treat doi: 10.1007/S10549-008-0272-2.
  • Bijl, M. J., Visser, L. E., Hofman, A., Vulto, A. G., van Gelder, T., Stricker, B. H. van Schaik, R. H. (2008). Influence of the CYP2D6*4 polymorphism on dose, switching, and discontinuation of antidepressants. Br J Clin Pharmacol 65:558–564.
  • Bijl, M. J., Visser, L. E., van Schaik, R. H., Kors, J. A., Witteman, J. C., Hofman, A., Vulto, A. G., van Gelder, T., Stricker, B. H. (2009b). Genetic variation in the CYP2D6 gene is associated with a lower heart rate and blood pressure in beta-blocker users. Clin Pharmacol Ther 85:45–50.
  • Birgersdotter, U. M., Wong, W., Turgeon, J. Roden, D. M. (1992). Stereoselective genetically-determined interaction between chronic flecainide and quinidine in patients with arrhythmias. Br J Clin Pharmacol 33:275–280.
  • Birkett, D. J., Rees, D., Andersson, T., Gonzalez, F. J., Miners, J. O. Veronese, M. E. (1994). In vitro proguanil activation to cycloguanil by human liver microsomes is mediated by CYP3A isoforms as well as by S-mephenytoin hydroxylase. Br J Clin Pharmacol 37:413–420.
  • Blaisdell, J., Jorge-Nebert, L. F., Coulter, S., Ferguson, S. S., Lee, S. J., Chanas, B., Xi, T., Mohrenweiser, H., Ghanayem, B. Goldstein, J. A. (2004). Discovery of new potentially defective alleles of human CYP2C9. Pharmacogenetics 14:527–537.
  • Blaisdell, J., Mohrenweiser, H., Jackson, J., Ferguson, S., Coulter, S., Chanas, B., Xi, T., Ghanayem, B. Goldstein, J. A. (2002). Identification and functional characterization of new potentially defective alleles of human CYP2C19. Pharmacogenetics 12:703–711.
  • Blanco, J. G., Edick, M. J., Hancock, M. L., Winick, N. J., Dervieux, T., Amylon, M. D., Bash, R. O., Behm, F. G., Camitta, B. M., Pui, C. H., Raimondi, S. C. Relling, M. V. (2002). Genetic polymorphisms in CYP3A5, CYP3A4, and NQO1 in children who developed therapy-related myeloid malignancies. Pharmacogenetics 12:605–611.
  • Bloomer, J. C., Woods, F. R., Haddock, R. E., Lennard, M. S. Tucker, G. T. (1992). The role of cytochrome P4502D6 in the metabolism of paroxetine by human liver microsomes. Br J Clin Pharmacol 33:521–523.
  • Blume, H., Donath, F., Warnke, A. Schug, B. S. (2006). Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Saf 29:769–784.
  • Blyden, G. T., Greenblatt, D. J., Scavone, J. M. Shader, R. I. (1986). Pharmacokinetics of diphenhydramine and a demethylated metabolite following intravenous and oral administration. J Clin Pharmacol 26:529–533.
  • Boberg, M., Angerbauer, R., Fey, P., Kanhai, W. K., Karl, W., Kern, A., Ploschke, J. Radtke, M. (1997). Metabolism of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic pathways and of cytochrome P450 isozymes involved. Drug Metab Dispos 25:321–331.
  • Bock, K. W., Schrenk, D., Forster, A., Griese, E. U., Morike, K., Brockmeier, D. Eichelbaum, M. (1994). The influence of environmental and genetic factors on CYP2D6, CYP1A2, and UDP-glucuronosyltransferases in man using sparteine, caffeine, and paracetamol as probes. Pharmacogenetics 4:209–218.
  • Bohanec Grabar, P., Rozman, B., Tomsic, M., Suput, D., Logar, D., Dolzan, V. (2008). Genetic polymorphism of CYP1A2 and the toxicity of leflunomide treatment in rheumatoid arthritis patients. Eur J Clin Pharmacol 64:871–876.
  • Bohets, H., Lavrijsen, K., Hendrickx, J., van Houdt, J., van Genechten, V., Verboven, P., Meuldermans, W., Heykants, J. (2000). Identification of the cytochrome P450 enzymes involved in the metabolism of cisapride: in vitro studies of potential co-medication interactions. Br J Pharmacol 129:1655–1667.
  • Bolaji, O. O., Coutts, R. T. Baker, G. B. (1993). Metabolism of trimipramine in vitro by human CYP2D6 isozyme. Res Commun Chem Pathol Pharmacol 82:111–120.
  • Bolaji, O. O., Sadare, I. O., Babalola, C. P. Ogunbona, F. A. (2002). Polymorphic oxidative metabolism of proguanil in a Nigerian population. Eur J Clin Pharmacol 58:543–545.
  • Bolton, J. L. Thatcher, G. R. (2008). Potential mechanisms of estrogen quinone carcinogenesis. Chem Res Toxicol 21:93–101.
  • Bon, M. A., Jansen Steur, E. N., de Vos, R. A. Vermes, I. (1999). Neurogenetic correlates of Parkinson’s disease: apolipoprotein-E and cytochrome P450 2D6 genetic polymorphism. Neurosci Lett 266:149–151.
  • Bonanni, B., Macis, D., Maisonneuve, P., Johansson, H. A., Gucciardo, G., Oliviero, P., Travaglini, R., Muraca, M. G., Rotmensz, N., Veronesi, U. Decensi, A. U. (2006). Polymorphism in the CYP2D6 tamoxifen-metabolizing gene influences clinical effect but not hot flashes: data from the Italian Tamoxifen Trial. J Clin Oncol 24:3708–3709; author reply, 3709.
  • Bondesson, U., Hartvig, P. Danielsson, B. (1981). Quantitative determination of the urinary excretion of ketobemidone and four of its metabolites after intravenous and oral administration in man. Drug Metab Dispos 9:376–380.
  • Bondolfi, G., Chautems, C., Rochat, B., Bertschy, G. Baumann, P. (1996). Nonresponse to citalopram in depressive patients: pharmacokinetic and clinical consequences of a fluvoxamine augmentation. Psychopharmacology (Berl) 128:421–425.
  • Bondolfi, G., Eap, C. B., Bertschy, G., Zullino, D., Vermeulen, A. Baumann, P. (2002). The effect of fluoxetine on the pharmacokinetics and safety of risperidone in psychotic patients. Pharmacopsychiatry 35:50–56.
  • Bonnabry, P., Leemann, T. Dayer, P. (1996). Role of human liver microsomal CYP2C9 in the biotransformation of lornoxicam. Eur J Clin Pharmacol 49:305–308.
  • Borg, K. O., Carlsson, E., Hoffmann, K. J., Jonsson, T. E., Thorin, H. Wallin, B. (1975). Metabolism of metoprolol-(3-h) in man, the dog, and the rat. Acta Pharmacol Toxicol (Copenh) 36:125–135.
  • Borges, S., Desta, Z., Li, L., Skaar, T. C., Ward, B. A., Nguyen, A., Jin, Y., Storniolo, A. M., Nikoloff, D. M., Wu, L., Hillman, G., Hayes, D. F., Stearns, V. Flockhart, D. A. (2006). Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 80:61–74.
  • Born, S. L., Caudill, D., Fliter, K. L. Purdon, M. P. (2002). Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. Drug Metab Dispos 30:483–487.
  • Bortkiewicz, A., Pilacik, B., Gadzicka, E. Szymczak, W. (2002). The excretion of 6-hydroxymelatonin sulfate in healthy young men exposed to electromagnetic fields emitted by cellular phone—an experimental study. Neuro Endocrinol Lett 23(Suppl 1):88–91.
  • Botsch, S., Gautier, J. C., Beaune, P., Eichelbaum, M. Kroemer, H. K. (1993). Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites. Mol Pharmacol 43:120–126.
  • Bottiger, Y., Dostert, P., Benedetti, M. S., Bani, M., Fiorentini, F., Casati, M., Poggesti, I., Alm, C., Alvan, G. Bertilsson, L. (1996). Involvement of CYP2D6 but not CYP2C19 in nicergoline metabolism in humans. Br J Clin Pharmacol 42:707–711.
  • Bottiger, Y., Tybring, G., Gotharson, E. Bertilsson, L. (1997). Inhibition of the sulfoxidation of omeprazole by ketoconazole in poor and extensive metabolizers of S-mephenytoin. Clin Pharmacol Ther 62:384–391.
  • Bourrie, M., Meunier, V., Berger, Y. Fabre, G. (1999). Role of cytochrome P-4502C9 in irbesartan oxidation by human liver microsomes. Drug Metab Dispos 27:288–296.
  • Boutroy, M. J., Vert, P., Royer, R. J., Monin, P. Royer-Morrot, M. J. (1979). Caffeine, a metabolite of theophylline during the treatment of apnea in the premature infant. J Pediatr 94:996–998.
  • Bovill, E. G., Fung, M. Cushman, M. (2004). Vitamin K and oral anticoagulation: thought for food. Am J Med 116:711–713.
  • Brachtendorf, L., Jetter, A., Beckurts, K. T., Holscher, A. H. Fuhr, U. (2002). Cytochrome P450 enzymes contributing to demethylation of maprotiline in man. Pharmacol Toxicol 90:144–149.
  • Braun, J., Kollert, J. R. Becker, J. U. (1987). Pharmacokinetics of flecainide in patients with mild and moderate renal failure compared with patients with normal renal function. Eur J Clin Pharmacol 31:711–714.
  • Brenner, S. S., Herrlinger, C., Dilger, K., Murdter, T. E., Hofmann, U., Marx, C. Klotz, U. (2003). Influence of age and cytochrome P450 2C9 genotype on the steady-state disposition of diclofenac and celecoxib. Clin Pharmacokinet 42:283–292.
  • Breyer-Pfaff, U., Fischer, D. Winne, D. (1997). Biphasic kinetics of quaternary ammonium glucuronide formation from amitriptyline and diphenhydramine in human liver microsomes. Drug Metab Dispos 25:340–345.
  • Breyer-Pfaff, U., Kroeker, M., Winkler, T. Kriemler, P. (1985). Isolation and identification of hydroxylated maprotiline metabolites. Xenobiotica 15:57–66.
  • Breyer-Pfaff, U., Pfandl, B., Nill, K., Nusser, E., Monney, C., Jonzier-Perey, M., Baettig, D. Baumann, P. (1992). Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. Clin Pharmacol Ther 52:350–358.
  • Brock, N., Hilgard, P., Peukert, M., Pohl, J. Sindermann, H. (1988). Basis and new developments in the field of oxazaphosphorines. Cancer Invest 6:513–532.
  • Brockmeyer, N. H., Breithaupt, H., Ferdinand, W., von Hattingberg, M., Ohnhaus, E. E. (1989). Kinetics of oral and intravenous mexiletine: lack of effect of cimetidine and ranitidine. Eur J Clin Pharmacol 36:375–378.
  • Brockmoller, J., Kirchheiner, J., Schmider, J., Walter, S., Sachse, C., Muller-Oerlinghausen, B. Roots, I. (2002). The impact of the CYP2D6 polymorphism on haloperidol pharmacokinetics and on the outcome of haloperidol treatment. Clin Pharmacol Ther 72:438–452.
  • Broly, F., Libersa, C., Lhermitte, M. Dupuis, B. (1990). Inhibitory studies of mexiletine and dextromethorphan oxidation in human liver microsomes. Biochem Pharmacol 39:1045–1053.
  • Broly, F., Marez, D., Lo Guidice, J. M., Sabbagh, N., Legrand, M., Boone, P. Meyer, U. A. (1995). A nonsense mutation in the cytochrome P450 CYP2D6 gene identified in a Caucasian with an enzyme deficiency. Hum Genet 96:601–603.
  • Broly, F. Meyer, U. A. (1993). Debrisoquine oxidation polymorphism: phenotypic consequences of a 3-base-pair deletion in exon 5 of the CYP2D6 gene. Pharmacogenetics 3:123–130.
  • Broly, F., Vandamme, N., Caron, J., Libersa, C. Lhermitte, M. (1991a). Single-dose quinidine treatment inhibits mexiletine oxidation in extensive metabolizers of debrisoquine. Life Sci 48:PL123–PL128.
  • Broly, F., Vandamme, N., Libersa, C. Lhermitte, M. (1991b). The metabolism of mexiletine in relation to the debrisoquine/sparteine-type polymorphism of drug oxidation. Br J Clin Pharmacol 32:459–466.
  • Brooks, B. A., McBride, O. W., Dolphin, C. T., Farrall, M., Scambler, P. J., Gonzalez, F. J. Idle, J. R. (1988). The gene CYP3 encoding P-450pcn1 (nifedipine oxidase) is tightly linked to the gene COL1A2 encoding collagen type 1 alpha on 7q21–q22.1. Am J Hum Genet 43:280–284.
  • Brosen, K., Klysner, R., Gram, L. F., Otton, S. V., Bech, P. Bertilsson, L. (1986a). Steady-state concentrations of imipramine and its metabolites in relation to the sparteine/debrisoquine polymorphism. Eur J Clin Pharmacol 30:679–684.
  • Brosen, K., Otton, S. V. Gram, L. F. (1986b). Imipramine demethylation and hydroxylation: impact of the sparteine oxidation phenotype. Clin Pharmacol Ther 40:543–549.
  • Brosen, K., Skjelbo, E. Flachs, H. (1993). Proguanil metabolism is determined by the mephenytoin oxidation polymorphism in Vietnamese living in Denmark. Br J Clin Pharmacol 36:105–108.
  • Brosen, K., Zeugin, T. Meyer, U. A. (1991). Role of P450IID6, the target of the sparteine-debrisoquin oxidation polymorphism, in the metabolism of imipramine. Clin Pharmacol Ther 49:609–617.
  • Brown, K. M., von Weymarn, L. B. Murphy, S. E. (2005). Identification of N-(hydroxymethyl) norcotinine as a major product of cytochrome P450 2A6, but not cytochrome P450 2A13-catalyzed cotinine metabolism. Chem Res Toxicol 18:1792–1798.
  • Brown, P. J., Bedard, L. L., Reid, K. R., Petsikas, D. Massey, T. E. (2007). Analysis of CYP2A contributions to metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human peripheral lung microsomes. Drug Metab Dispos 35:2086–2094.
  • Bruno, R., Vivier, N., Montay, G., Le Liboux, A., Powe, L. K., Delumeau, J. C. Rhodes, G. R. (1997). Population pharmacokinetics of riluzole in patients with amyotrophic lateral sclerosis. Clin Pharmacol Ther 62:518–526.
  • Brynne, N., Dalen, P., Alvan, G., Bertilsson, L. Gabrielsson, J. (1998). Influence of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamic of tolterodine. Clin Pharmacol Ther 63:529–539.
  • Bryson, H. M. Benfield, P. (1997). Donepezil. Drugs Aging 10:234–239; discussion, 240–231.
  • Bryson, H. M., Fulton, B. Benfield, P. (1996). Riluzole. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in amyotrophic lateral sclerosis. Drugs 52:549–563.
  • Bryson, H. M., Fulton, B. R. Faulds, D. (1995). Propofol. An update of its use in anaesthesia and conscious sedation. Drugs 50:513–559.
  • Bryson, H. M., Palmer, K. J., Langtry, H. D. Fitton, A. (1993). Propafenone. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias. Drugs 45:85–130.
  • Buchert, E. Woosley, R. L. (1992). Clinical implications of variable antiarrhythmic drug metabolism. Pharmacogenetics 2:2–11.
  • Bulat, V., Lugovic, L., Situm, M., Buljan, M. Bradic, L. (2007). Porphyria cutanea tarda as the most common porphyria. Acta Dermatovenerol Croat 15:254–263.
  • Burger, D., van der Heiden I., la Porte, C., van der Ende, M., Groeneveld, P., Richter, C., Koopmans, P., Kroon, F., Sprenger, H., Lindemans, J., Schenk, P., van Schaik, R. (2006). Interpatient variability in the pharmacokinetics of the HIV non-nucleoside reverse transcriptase inhibitor efavirenz: the effect of gender, race, and CYP2B6 polymorphism. Br J Clin Pharmacol 61:148–154.
  • Burger, D. M., Prins, J. M., van der Ende, M. E. Aarnoutse, R. E. (2004). The effect of nevirapine on the pharmacokinetics of indinavir/ritonavir 800/100 mg BID. J Acquir Immune Defic Syndr 35:97–98.
  • Bussey, H. I., Wittkowsky, A. K., Hylek, E. M. Walker, M. B. (2008). Genetic testing for warfarin dosing? Not yet ready for prime time. Pharmacotherapy 28:141–143.
  • Butler, M. A., Lang, N. P., Young, J. F., Caporaso, N. E., Vineis, P., Hayes, R. B., Teitel, C. H., Massengill, J. P., Lawsen, M. F. Kadlubar, F. F. (1992). Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 2:116–127.
  • Buzdar, A., Hayes, D., El-Khoudary, A., Yan, S., Lonning, P., Lichinitser, M., Gopal, R., Falkson, G., Pritchard, K., Lipton, A., Wolter, K., Lee, A., Fly, K., Chew, R., Alderdice, M., Burke, K. Eisenber, P. (2002). Phase III randomized trial of droloxifene and tamoxifen as first-line endocrine treatment of ER/PgR-positive advanced breast cancer. Breast Cancer Res Treat 73:161–175.
  • Byerly, M. J. DeVane, C. L. (1996). Pharmacokinetics of clozapine and risperidone: a review of recent literature. J Clin Psychopharmacol 16:177–187.
  • Bylund, D. B. (1981). Interactions of neuroleptic metabolites with dopaminergic, alpha adrenergic, and muscarinic cholinergic receptors. J Pharmacol Exp Ther 217:81–86.
  • Bylund, J., Kunz, T., Valmsen, K. Oliw, E. H. (1998). Cytochromes P450 with bisallylic hydroxylation activity on arachidonic and linoleic acids studied with human recombinant enzymes and with human and rat liver microsomes. J Pharmacol Exp Ther 284:51–60.
  • Cacabelos, R. (2008). Pharmacogenomics in Alzheimer’s disease. Methods Mol Biol 448:213–357.
  • Cai, W. M., Chen, B., Cai, M. H., Chen, Y. Zhang, Y. D. (1999a). The influence of CYP2D6 activity on the kinetics of propafenone enantiomers in Chinese subjects. Br J Clin Pharmacol 47:553–556.
  • Cai, W. M., Chen, B., Zhou, Y. Zhang, Y. D. (1999b). Fluoxetine impairs the CYP2D6-mediated metabolism of propafenone enantiomers in healthy Chinese volunteers. Clin Pharmacol Ther 66:516–521.
  • Cai, W. M., Nikoloff, D. M., Pan, R. M., de Leon, J., Fanti, P., Fairchild, M., Koch, W. H. Wedlund, P. J. (2006). CYP2D6 genetic variation in healthy adults and psychiatric African-American subjects: implications for clinical practice and genetic testing. Pharmacogenomics J 6:343–350.
  • Campbell, M. E., Grant, D. M., Inaba, T. Kalow, W. (1987). Biotransformation of caffeine, paraxanthine, theophylline, and theobromine by polycyclic aromatic hydrocarbon-inducible cytochrome(s) P-450 in human liver microsomes. Drug Metab Dispos 15:237–249.
  • Campbell, N. P., Kelly, J. G., Adgey, A. A. Shanks, R. G. (1978). The clinical pharmacology of mexiletine. Br J Clin Pharmacol 6:103–108.
  • Cano, J. P. Sumirtapura, Y. C. (1981). [Comparative pharmacokinetics of diazepam and flunitrazepam]. Ann Anesthesiol Fr 22:175–179.
  • Caporaso, N. E., Lerman, C., Audrain, J., Boyd, N. R., Main, D., Issaq, H. J., Utermahlan, B., Falk, R. T. Shields, P. (2001). Nicotine metabolism and CYP2D6 phenotype in smokers. Cancer Epidemiol Biomarkers Prev 10:261–263.
  • Capucci, A., Boriani, G., Marchesini, B., Strocchi, E., Tomasi, L., Balducelli, M., Frabetti, L., Ambrosioni, E. Magnani, B. (1990). Minimal effective concentration values of propafenone and 5-hydroxy-propafenone in acute and chronic therapy. Cardiovasc Drugs Ther 4:281–287.
  • Caraco, Y., Muszkat, M. Wood, A. J. (2001). Phenytoin metabolic ratio: a putative marker of CYP2C9 activity in vivo. Pharmacogenetics 11:587–596.
  • Caraco, Y., Sheller, J. Wood, A. J. (1996). Pharmacogenetic determination of the effects of codeine and prediction of drug interactions. J Pharmacol Exp Ther 278:1165–1174.
  • Carcillo, J. A., Adedoyin, A., Burckart, G. J., Frye, R. F., Venkataramanan, R., Knoll, C., Thummel, K., Roskos, L., Wilson, J. W., Sereika, S., Romkes, M., Bebia, Z. Branch, R. A. (2003). Coordinated intrahepatic and extrahepatic regulation of cytochrome p4502D6 in healthy subjects and in patients after liver transplantation. Clin Pharmacol Ther 73:456–467.
  • Carey, E. L., Jr., Duff, H. J., Roden, D. M., Primm, R. K., Wilkinson, G. R., Wang, T., Oates, J. A. Woosley, R. L. (1984). Encainide and its metabolites. Comparative effects in man on ventricular arrhythmia and electrocardiographic intervals. J Clin Invest 73:539–547.
  • Carmo, H., Brulport, M., Hermes, M., Oesch, F., Silva, R., Ferreira, L. M., Branco, P. S., Boer, D., Remiao, F., Carvalho, F., Schon, M. R., Krebsfaenger, N., Doehmer, J., Bastos Mde, L., Hengstler, J. G. (2006). Influence of CYP2D6 polymorphism on 3,4-methylenedioxymethamphetamine (“Ecstasy”) cytotoxicity. Pharmacogenet Genomics 16:789–799.
  • Carrillo, J. A., Dahl, M. L., Svensson, J. O., Alm, C., Rodriguez, I. Bertilsson, L. (1996). Disposition of fluvoxamine in humans is determined by the polymorphic CYP2D6 and also by the CYP1A2 activity. Clin Pharmacol Ther 60:183–190.
  • Carter, S. J., Li, X. F., Mackey, J. R., Modi, S., Hanson, J. Dovichi, N. J. (2001). Biomonitoring of urinary tamoxifen and its metabolites from breast cancer patients using nonaqueous capillary electrophoresis with electrospray mass spectrometry. Electrophoresis 22:2730–2736.
  • Casado, J. L., Dronda, F., Hertogs, K., Sabido, R., Antela, A., Marti-Belda, P., Dehertogh, P. Moreno, S. (2001). Efficacy, tolerance, and pharmacokinetics of the combination of stavudine, nevirapine, nelfinavir, and saquinavir as salvage regimen after ritonavir or indinavir failure. AIDS Res Hum Retroviruses 17:93–98.
  • Cascorbi, I. (2003). Pharmacogenetics of cytochrome p4502D6: genetic background and clinical implication. Eur J Clin Invest 33:17–22.
  • Cascorbi, I., Brockmoller, J. Roots, I. (1996). A C4887A polymorphism in exon 7 of human CYP1A1: population frequency, mutation linkages, and impact on lung cancer susceptibility. Cancer Res 56:4965–4969.
  • Cashman, J. R., Celestial, J. R. Leach, A. R. (1992a). Enantioselective N-oxygenation of chlorpheniramine by the flavin-containing monooxygenase from hog liver. Xenobiotica 22:459–469.
  • Cashman, J. R., Park, S. B., Yang, Z. C., Wrighton, S. A., Jacob, P., 3rd, Benowitz, N. L. (1992b). Metabolism of nicotine by human liver microsomes: stereoselective formation of trans-nicotine N’-oxide. Chem Res Toxicol 5:639–646.
  • Cath, D. C., Gijsman, H. J., Schoemaker, R. C., van Griensven, J. M., Troost, N., van Kempen, G. M. Cohen, A. F. (1999). The effect of m-CPP on tics and obsessive-compulsive phenomena in Gilles de la Tourette syndrome. Psychopharmacology (Berl) 144:137–143.
  • Catteau, A., Bechtel, Y. C., Poisson, N., Bechtel, P. R. Bonaiti-Pellie, C. (1995). A population and family study of CYP1A2 using caffeine urinary metabolites. Eur J Clin Pharmacol 47:423–430.
  • Cauffiez, C., Lo-Guidice, J. M., Quaranta, S., Allorge, D., Chevalier, D., Cenee, S., Hamdan, R., Lhermitte, M., Lafitte, J. J., Libersa, C., Colombel, J. F., Stucker, I. Broly, F. (2004). Genetic polymorphism of the human cytochrome CYP2A13 in a French population: implication in lung cancer susceptibility. Biochem Biophys Res Commun 317:662–669.
  • Cauffiez, C., Pottier, N., Tournel, G., Lo-Guidice, J. M., Allorge, D., Chevalier, D., Migot-Nabias, F., Kenani, A. Broly, F. (2005). CYP2A13 genetic polymorphism in French Caucasian, Gabonese, and Tunisian populations. Xenobiotica 35:661–669.
  • Cavaco, I., Piedade, R., Gil, J. P. Ribeiro, V. (2006). CYP2C8 polymorphism among the Portuguese. Clin Chem Lab Med 44:168–170.
  • Cavalieri, E. L. Rogan, E. G. (1992). The approach to understanding aromatic hydrocarbon carcinogenesis. The central role of radical cations in metabolic activation. Pharmacol Ther 55:183–199.
  • Cavalieri, E. L. Rogan, E. G. (1995). Central role of radical cations in metabolic activation of polycyclic aromatic hydrocarbons. Xenobiotica 25:677–688.
  • Cavalli, A., Maggioni, A. P., Marchi, S., Volpi, A. Latini, R. (1988). Flecainide half-life prolongation in 2 patients with congestive heart failure and complex ventricular arrhythmias. Clin Pharmacokinet 14:187–188.
  • Cazaubon, C., Gougat, J., Bousquet, F., Guiraudou, P., Gayraud, R., Lacour, C., Roccon, A., Galindo, G., Barthelemy, G., Gautret, B. et al. (1993). Pharmacological characterization of SR 47436, a new nonpeptide AT1 subtype angiotensin II receptor antagonist. J Pharmacol Exp Ther 265:826–834.
  • Cervilla, J. A., Russ, C., Holmes, C., Aitchison, K., Smith, C. A., Powell, J. Lovestone, S. (1999). CYP2D6 polymorphisms in Alzheimer’s disease, with and without extrapyramidal signs, showing no apolipoprotein E epsilon 4 effect modification. Biol Psychiatry 45:426–429.
  • Chander, S. K., McCague, R., Luqmani, Y., Newton, C., Dowsett, M., Jarman, M. Coombes, R. C. (1991). Pyrrolidino-4-iodotamoxifen and 4-iodotamoxifen, new analogues of the antiestrogen tamoxifen for the treatment of breast cancer. Cancer Res 51:5851–5858.
  • Chando, T. J., Everett, D. W., Kahle, A. D., Starrett, A. M., Vachharajani, N., Shyu, W. C., Kripalani, K. J. Barbhaiya, R. H. (1998). Biotransformation of irbesartan in man. Drug Metab Dispos 26:408–417.
  • Chang, B. L., Zheng, S. L., Isaacs, S. D., Turner, A., Hawkins, G. A., Wiley, K. E., Bleecker, E. R., Walsh, P. C., Meyers, D. A., Isaacs, W. B. Xu, J. (2003a). Polymorphisms in the CYP1A1 gene are associated with prostate cancer risk. Int J Cancer 106:375–378.
  • Chang, T., Okerholm, R. A. Glazko, A. J. (1974). Identification of diphenydramine (Benadryl) metabolities in human subjects. Res Commun Chem Pathol Pharmacol 9:391–404.
  • Chang, T. K., Bandiera, S. M. Chen, J. (2003b). Constitutive androstane receptor and pregnane X receptor gene expression in human liver: interindividual variability and correlation with CYP2B6 mRNA levels. Drug Metab Dispos 31:7–10.
  • Chang, T. K., Weber, G. F., Crespi, C. L. Waxman, D. J. (1993). Differential activation of cyclophosphamide and ifosphamide by cytochromes P-450 2B and 3A in human liver microsomes. Cancer Res 53:5629–5637.
  • Charlier, C., Broly, F., Lhermitte, M., Pinto, E., Ansseau, M. Plomteux, G. (2003). Polymorphisms in the CYP 2D6 gene: association with plasma concentrations of fluoxetine and paroxetine. Ther Drug Monit 25:738–742.
  • Chen, B. Cai, W. M. (2003). Influence of CYP2D6*10B genotype on pharmacokinetics of propafenone enantiomers in Chinese subjects. Acta Pharmacol Sin 24:1277–1280.
  • Chen, C., Meng, L., Ma, X., Krausz, K. W., Pommier, Y., Idle, J. R. Gonzalez, F. J. (2006a). Urinary metabolite profiling reveals CYP1A2-mediated metabolism of NSC686288 (aminoflavone). J Pharmacol Exp Ther 318:1330–1342.
  • Chen, C. S., Lin, J. T., Goss, K. A., He, Y. A., Halpert, J. R. Waxman, D. J. (2004). Activation of the anticancer prodrugs cyclophosphamide and ifosfamide: identification of cytochrome P450 2B enzymes and site-specific mutants with improved enzyme kinetics. Mol Pharmacol 65:1278–1285.
  • Chen, G., Blevins-Primeau, A. S., Dellinger, R. W., Muscat, J. E. Lazarus, P. (2007). Glucuronidation of nicotine and cotinine by UGT2B10: loss of function by the UGT2B10 Codon 67 (Asp>Tyr) polymorphism. Cancer Res 67:9024–9029.
  • Chen, G. F., Tang, Y. M., Green, B., Lin, D. X., Guengerich, F. P., Daly, A. K., Caporaso, N. E. Kadlubar, F. F. (1999). Low frequency of CYP2A6 gene polymorphism as revealed by a one-step polymerase chain reaction method. Pharmacogenetics 9:327–332.
  • Chen, L., Qin, S., Xie, J., Tang, J., Yang, L., Shen, W., Zhao, X., Du, J., He, G., Feng, G., He, L. Xing, Q. (2008). Genetic polymorphism analysis of CYP2C19 in Chinese Han populations from different geographic areas of mainland China. Pharmacogenomics 9:691–702.
  • Chen, X., Wang, H., Xie, W., Liang, R., Wei, Z., Zhi, L., Zhang, X., Hao, B., Zhong, S., Zhou, G., Zhang, L., Gao, X., Zhu, Y. He, F. (2006b). Association of CYP1A2 genetic polymorphisms with hepatocellular carcinoma susceptibility: a case-control study in a high-risk region of China. Pharmacogenet Genomics 16:219–227.
  • Chen, X., Wang, L., Zhi, L., Zhou, G., Wang, H., Zhang, X., Hao, B., Zhu, Y., Cheng, Z. He, F. (2005). The G-113A polymorphism in CYP1A2 affects the caffeine metabolic ratio in a Chinese population. Clin Pharmacol Ther 78:249–259.
  • Chen, X., Xia, Y., Alford, M., DeTeresa, R., Hansen, L., Klauber, M. R., Katzman, R., Thal, L., Masliah, E. Saitoh, T. (1995). The CYP2D6B allele is associated with a milder synaptic pathology in Alzheimer’s disease. Ann Neurol 38:653–658.
  • Chen, X., Zhong, D. Blume, H. (2000). Stereoselective pharmacokinetics of propafenone and its major metabolites in healthy Chinese volunteers. Eur J Pharm Sci 10:11–16.
  • Chevalier, D., Cauffiez, C., Allorge, D., Lo-Guidice, J. M., Lhermitte, M., Lafitte, J. J. Broly, F. (2001). Five novel natural allelic variants-951A>C, 1042G>A (D348N), 1156A>T (I386F), 1217G>A (C406Y) and 1291C>T (C431Y)-of the human CYP1A2 gene in a French Caucasian population. Hum Mutat 17:355–356.
  • Chida, M., Ariyoshi, N., Yokoi, T., Nemoto, N., Inaba, M., Kinoshita, M. Kamataki, T. (2002). New allelic arrangement CYP2D6*36 × 2 found in a Japanese poor metabolizer of debrisoquine. Pharmacogenetics 12:659–662.
  • Chida, M., Yokoi, T., Fukui, T., Kinoshita, M., Yokota, J. Kamataki, T. (1999a). Detection of three genetic polymorphisms in the 5’-flanking region and intron 1 of human CYP1A2 in the Japanese population. Jpn J Cancer Res 90:899–902.
  • Chida, M., Yokoi, T., Nemoto, N., Inaba, M., Kinoshita, M. Kamataki, T. (1999b). A new variant CYP2D6 allele (CYP2D6*21) with a single base insertion in exon 5 in a Japanese population associated with a poor metabolizer phenotype. Pharmacogenetics 9:287–293.
  • Chinta, S. J., Pai, H. V., Upadhya, S. C., Boyd, M. R. Ravindranath, V. (2002). Constitutive expression and localization of the major drug metabolizing enzyme, cytochrome P4502D in human brain. Brain Res Mol Brain Res 103:49–61.
  • Cho, J. Y., Yu, K. S., Jang, I. J., Yang, B. H., Shin, S. G. Yim, D. S. (2002). Omeprazole hydroxylation is inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19. Br J Clin Pharmacol 53:393–397.
  • Cholerton, S., Arpanahi, A., McCracken, N., Boustead, C., Taber, H., Johnstone, E., Leathart, J., Daly, A. K. Idle, J. R. (1994). Poor metabolisers of nicotine and CYP2D6 polymorphism. Lancet 343:62–63.
  • Chou, F. C., Tzeng, S. J. Huang, J. D. (2001). Genetic polymorphism of cytochrome P450 3A5 in Chinese. Drug Metab Dispos 29:1205–1209.
  • Chow, T., Hiroi, T., Imaoka, S., Chiba, K. Funae, Y. (1999). Isoform-selective metabolism of mianserin by cytochrome P-450 2D. Drug Metab Dispos 27:1200–1204.
  • Chowbay, B., Cumaraswamy, S., Cheung, Y. B., Zhou, Q. Lee, E. J. (2003). Genetic polymorphisms in MDR1 and CYP3A4 genes in Asians and the influence of MDR1 haplotypes on cyclosporin disposition in heart transplant recipients. Pharmacogenetics 13:89–95.
  • Chowbay, B., Zhou, S. Lee, E. J. (2005). An interethnic comparison of polymorphisms of the genes encoding drug-metabolizing enzymes and drug transporters: experience in Singapore. Drug Metab Rev 37:327–378.
  • Christensen, M., Tybring, G., Mihara, K., Yasui-Furokori, N., Carrillo, J. A., Ramos, S. I., Andersson, K., Dahl, M. L. Bertilsson, L. (2002). Low daily 10-mg and 20-mg doses of fluvoxamine inhibit the metabolism of both caffeine (cytochrome P4501A2) and omeprazole (cytochrome P4502C19). Clin Pharmacol Ther 71:141–152.
  • Christensen, M. L., Meibohm, B., Capparelli, E. V., Velasquez-Mieyer, P., Burghen, G. A. Tamborlane, W. V. (2005). Single- and multiple-dose pharmacokinetics of pioglitazone in adolescents with type 2 diabetes. J Clin Pharmacol 45:1137–1144.
  • Christiansen, L., Bygum, A., Jensen, A., Thomsen, K., Brandrup, F., Horder, M. Petersen, N. E. (2000). Association between CYP1A2 polymorphism and susceptibility to porphyria cutanea tarda. Hum Genet 107:612–614.
  • Clarke, S. M., Mulcahy, F. M., Tjia, J., Reynolds, H. E., Gibbons, S. E., Barry, M. G. Back, D. J. (2001). Pharmacokinetic interactions of nevirapine and methadone and guidelines for use of nevirapine to treat injection drug users. Clin Infect Dis 33:1595–1597.
  • Clarke, T. A. Waskell, L. A. (2003). The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Drug Metab Dispos 31:53–59.
  • Cobb, M. N., Desai, J., Brown, L. S., Jr., Zannikos, P. N. Rainey, P. M. (1998). The effect of fluconazole on the clinical pharmacokinetics of methadone. Clin Pharmacol Ther 63:655–662.
  • Code, E. L., Crespi, C. L., Penman, B. W., Gonzalez, F. J., Chang, T. K. Waxman, D. J. (1997). Human cytochrome P4502B6: interindividual hepatic expression, substrate specificity, and role in procarcinogen activation. Drug Metab Dispos 25:985–993.
  • Coffman, B. L., Rios, G. R., King, C. D. Tephly, T. R. (1997). Human UGT2B7 catalyzes morphine glucuronidation. Drug Metab Dispos 25:1–4.
  • Cohen, K., van Cutsem, G., Boulle, A., McIlleron, H., Goemaere, E., Smith, P. J. Maartens, G. (2008). Effect of rifampicin-based antitubercular therapy on nevirapine plasma concentrations in South African adults with HIV-associated tuberculosis. J Antimicrob Chemother 61:389–393.
  • Cohen, S., Lhuillier, F., Mouloua, Y., Vignal, B., Favetta, P. Guitton, J. (2007). Quantitative measurement of propofol and in main glucuroconjugate metabolites in human plasma using solid phase extraction-liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 854:165–172.
  • Coleman, T., Ellis, S. W., Martin, I. J., Lennard, M. S. Tucker, G. T. (1996). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is N-demethylated by cytochromes P450 2D6, 1A2 and 3A4—implications for susceptibility to Parkinson’s disease. J Pharmacol Exp Ther 277:685–690.
  • Coles, R. Kharasch, E. D. (2007). Stereoselective analysis of bupropion and hydroxybupropion in human plasma and urine by LC/MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 857:67–75.
  • Coller, J. K., Somogyi, A. A. Bochner, F. (1999a). Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol 48:158–167.
  • Coller, J. K., Somogyi, A. A. Bochner, F. (1999b). Flunitrazepam oxidative metabolism in human liver microsomes: involvement of CYP2C19 and CYP3A4. Xenobiotica 29:973–986.
  • Colvin, O. M. (1999). An overview of cyclophosphamide development and clinical applications. Curr Pharm Des 5:555–560.
  • Comoglio, A., Gibbs, A. H., White, I. N., Gant, T., Martin, E. A., Smith, L. L., Gamalero, S. R. DeMatteis, F. (1996). Effect of tamoxifen feeding on metabolic activation of tamoxifen by the liver of the rhesus monkey: does liver accumulation of inhibitory metabolites protect from tamoxifen-dependent genotoxicity and cancer? Carcinogenesis 17:1687–1693.
  • Conard, G. J., Carlson, G. L., Frost, J. W., Ober, R. E., Leon, A. S. Hunninghake, D. B. (1984). Plasma concentrations of flecainide acetate, a new antiarrhythmic agent, in humans. Clin Ther 6:643–652.
  • Conn, P. J. Sanders-Bush, E. (1987). Relative efficacies of piperazines at the phosphoinositide hydrolysis-linked serotonergic (5-HT-2 and 5-HT-1c) receptors. J Pharmacol Exp Ther 242:552–557.
  • Connolly, S. J., Kates, R. E., Lebsack, C. S., Harrison, D. C. Winkle, R. A. (1983). Clinical pharmacology of propafenone. Circulation 68:589–596.
  • Contin, M., Sangiorgi, S., Riva, R., Parmeggiani, A., Albani, F. Baruzzi, A. (2002). Evidence of polymorphic CYP2C19 involvement in the human metabolism of N-desmethylclobazam. Ther Drug Monit 24:737–741.
  • Coombes, R. C., Haynes, B. P., Dowsett, M., Quigley, M., English, J., Judson, I. R., Griggs, L. J., Potter, G. A., McCague, R. Jarman, M. (1995). Idoxifene: report of a phase I study in patients with metastatic breast cancer. Cancer Res 55:1070–1074.
  • Corchero, J., Granvil, C. P., Akiyama, T. E., Hayhurst, G. P., Pimprale, S., Feigenbaum, L., Idle, J. R. Gonzalez, F. J. (2001a). The CYP2D6 humanized mouse: effect of the human CYP2D6 transgene and HNF4alpha on the disposition of debrisoquine in the mouse. Mol Pharmacol 60:1260–1267.
  • Corchero, J., Pimprale, S., Kimura, S. Gonzalez, F. J. (2001b). Organization of the CYP1A cluster on human chromosome 15: implications for gene regulation. Pharmacogenetics 11:1–6.
  • Cornelis, M. C., El-Sohemy, A., Kabagambe, E. K. Campos, H. (2006). Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 295:1135–1141.
  • Cosma, G., Crofts, F., Taioli, E., Toniolo, P. Garte, S. (1993). Relationship between genotype and function of the human CYP1A1 gene. J Toxicol Environ Health 40:309–316.
  • Court, M. H., Duan, S. X., Guillemette, C., Journault, K., Krishnaswamy, S., Von Moltke, L. L. Greenblatt, D. J. (2002). Stereoselective conjugation of oxazepam by human UDP-glucuronosyltransferases (UGTs): S-oxazepam is glucuronidated by UGT2B15, while R-oxazepam is glucuronidated by UGT2B7 and UGT1A9. Drug Metab Dispos 30:1257–1265.
  • Court, M. H., Duan, S. X., Hesse, L. M., Venkatakrishnan, K. Greenblatt, D. J. (2001). Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Anesthesiology 94:110–119.
  • Court, M. H., Hao, Q., Krishnaswamy, S., Bekaii-Saab, T., Al-Rohaimi, A., von Moltke, L. L. Greenblatt, D. J. (2004). UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver. J Pharmacol Exp Ther 310:656–665.
  • Cox, P. J., Ryan, D. A., Hollis, F. J., Harris, A. M., Miller, A. K., Vousden, M. Cowley, H. (2000). Absorption, disposition, and metabolism of rosiglitazone, a potent thiazolidinedione insulin sensitizer, in humans. Drug Metab Dispos 28:772–780.
  • Crespi, C. L. Miller, V. P. (1997). The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. Pharmacogenetics 7:203–210.
  • Crespi, C. L., Penman, B. W., Leakey, J. A., Arlotto, M. P., Stark, A., Parkinson, A., Turner, T., Steimel, D. T., Rudo, K., Davies, R. L. et al. (1990). Human cytochrome P450IIA3: cDNA sequence, role of the enzyme in the metabolic activation of promutagens, comparison to nitrosamine activation by human cytochrome P450IIE1. Carcinogenesis 11:1293–1300.
  • Crespi, C. L., Penman, B. W., Steimel, D. T., Smith, T., Yang, C. S. Sutter, T. R. (1997). Development of a human lymphoblastoid cell line constitutively expressing human CYP1B1 cDNA: substrate specificity with model substrates and promutagens. Mutagenesis 12:83–89.
  • Cresteil, T., Monsarrat, B., Dubois, J., Sonnier, M., Alvinerie, P. Gueritte, F. (2002). Regioselective metabolism of taxoids by human CYP3A4 and 2C8: structure-activity relationship. Drug Metab Dispos 30:438–445.
  • Crettol, S., Deglon, J. J., Besson, J., Croquette-Krokar, M., Hammig, R., Gothuey, I., Monnat, M. Eap, C. B. (2006). ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment. Clin Pharmacol Ther 80:668–681.
  • Crettol, S., Deglon, J. J., Besson, J., Croquette-Krokkar, M., Gothuey, I., Hammig, R., Monnat, M., Huttemann, H., Baumann, P. Eap, C. B. (2005). Methadone enantiomer plasma levels, CYP2B6, CYP2C19, and CYP2C9 genotypes, and response to treatment. Clin Pharmacol Ther 78:593–604.
  • Crewe, H. K., Ellis, S. W., Lennard, M. S. Tucker, G. T. (1997). Variable contribution of cytochromes P450 2D6, 2C9, and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes. Biochem Pharmacol 53:171–178.
  • Crewe, H. K., Lennard, M. S., Tucker, G. T., Woods, F. R. Haddock, R. E. (1992). The effect of selective serotonin reuptake inhibitors on cytochrome P4502D6 (CYP2D6) activity in human liver microsomes. Br J Clin Pharmacol 34:262–265.
  • Crewe, H. K., Notley, L. M., Wunsch, R. M., Lennard, M. S. Gillam, E. M. (2002). Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4’-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos 30:869–874.
  • D’Agostino, J., Zhang, X., Wu, H., Ling, G., Wang, S., Zhang, Q. Y., Liu, F. Ding, X. (2008). Characterization of CYP2A13*2, a variant cytochrome P450 allele previously found to be associated with decreased incidences of lung adenocarcinoma in smokers. Drug Metab Dispos 36:2316–2323.
  • Dahl-Puustinen, M. L., Liden, A., Alm, C., Nordin, C. Bertilsson, L. (1989). Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings. Clin Pharmacol Ther 46:78–81.
  • Dahl, M. L., Bertilsson, L. Nordin, C. (1996). Steady-state plasma levels of nortriptyline and its 10-hydroxy metabolite: relationship to the CYP2D6 genotype. Psychopharmacology (Berl) 123:315–319.
  • Dahl, M. L., Johansson, I., Bertilsson, L., Ingelman-Sundberg, M. Sjoqvist, F. (1995a). Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis. J Pharmacol Exp Ther 274:516–520.
  • Dahl, M. L., Johansson, I., Palmertz, M. P., Ingelman-Sundberg, M. Sjoqvist, F. (1992). Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population. Clin Pharmacol Ther 51:12–17.
  • Dahl, M. L., Nordin, C. Bertilsson, L. (1991). Enantioselective hydroxylation of nortriptyline in human liver microsomes, intestinal homogenate, and patients treated with nortriptyline. Ther Drug Monit 13:189–194.
  • Dahl, M. L., Tybring, G., Elwin, C. E., Alm, C., Andreasson, K., Gyllenpalm, M. Bertilsson, L. (1994). Stereoselective disposition of mianserin is related to debrisoquin hydroxylation polymorphism. Clin Pharmacol Ther 56:176–183.
  • Dahl, M. L., Yue, Q. Y., Roh, H. K., Johansson, I., Sawe, J., Sjoqvist, F. Bertilsson, L. (1995b). Genetic analysis of the CYP2D locus in relation to debrisoquine hydroxylation capacity in Korean, Japanese, and Chinese subjects. Pharmacogenetics 5:159–164.
  • Dahri, K. Ensom, M. H. (2007). Efavirenz and nevirapine in HIV-1 infection: is there a role for clinical pharmacokinetic monitoring? Clin Pharmacokinet 46:109–132.
  • Dai, D., Tang, J., Rose, R., Hodgson, E., Bienstock, R. J., Mohrenweiser, H. W. Goldstein, J. A. (2001a). Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther 299:825–831.
  • Dai, D., Zeldin, D. C., Blaisdell, J. A., Chanas, B., Coulter, S. J., Ghanayem, B. I. Goldstein, J. A. (2001b). Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics 11:597–607.
  • Daigo, S., Takahashi, Y., Fujieda, M., Ariyoshi, N., Yamazaki, H., Koizumi, W., Tanabe, S., Saigenji, K., Nagayama, S., Ikeda, K., Nishioka, Y. Kamataki, T. (2002). A novel mutant allele of the CYP2A6 gene (CYP2A6*11 ) found in a cancer patient who showed poor metabolic phenotype towards tegafur. Pharmacogenetics 12:299–306.
  • Dailly, E., Reliquet, V., Raffi, F. Jolliet, P. (2005). A population approach to study the influence of nevirapine administration on lopinavir pharmacokinetics in HIV-1 infected patients. Eur J Clin Pharmacol 61:153–156.
  • Dailly, E., Tribut, O., Tattevin, P., Arvieux, C., Perre, P., Raffi, F. Jolliet, P. (2006). Influence of tenofovir, nevirapine, and efavirenz on ritonavir-boosted atazanavir pharmacokinetics in HIV-infected patients. Eur J Clin Pharmacol 62:523–526.
  • Dain, J. G., Fu, E., Gorski, J., Nicoletti, J. Scallen, T. J. (1993). Biotransformation of fluvastatin sodium in humans. Drug Metab Dispos 21:567–572.
  • Dalen, P., Dahl, M. L., Bernal Ruiz, M. L., Nordin, J. Bertilsson, L. (1998). 10-hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin Pharmacol Ther 63:444–452.
  • Dalvie, D. K. O’Connell, T. N. (2004). Characterization of novel dihydrothienopyridinium and thienopyridinium metabolites of ticlopidine in vitro: role of peroxidases, cytochromes p450, and monoamine oxidases. Drug Metab Dispos 32:49–57.
  • Daly, A. K., Brockmoller, J., Broly, F., Eichelbaum, M., Evans, W. E., Gonzalez, F. J., Huang, J. D., Idle, J. R., Ingelman-Sundberg, M., Ishizaki, T., Jacqz-Aigrain, E., Meyer, U. A., Nebert, D. W., Steen, V. M., Wolf, C. R. Zanger, U. M. (1996a). Nomenclature for human CYP2D6 alleles. Pharmacogenetics 6:193–201.
  • Daly, A. K., Fairbrother, K. S., Andreassen, O. A., London, S. J., Idle, J. R. Steen, V. M. (1996b). Characterization and PCR-based detection of two different hybrid CYP2D7P/CYP2D6 alleles associated with the poor metabolizer phenotype. Pharmacogenetics 6:319–328.
  • Daly, A. K., Leathart, J. B., London, S. J. Idle, J. R. (1995). An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution. Hum Genet 95:337–341.
  • Dang, M. T., Hambleton, J. Kayser, S. R. (2005). The influence of ethnicity on warfarin dosage requirement. Ann Pharmacother 39:1008–1012.
  • Danilo, P.Jr., (1979). Aprindine. Am Heart J 97:119–124.
  • Dasaradhi, L. Shibutani, S. (1997). Identification of tamoxifen-DNA adducts formed by alpha-sulfate tamoxifen and alpha-acetoxytamoxifen. Chem Res Toxicol 10:189–196.
  • Davi, H., Tronquet, C., Miscoria, G., Perrier, L., DuPont, P., Caix, J., Simiand, J. Berger, Y. (2000). Disposition of irbesartan, an angiotensin II AT1-receptor antagonist, in mice, rats, rabbits, and macaques. Drug Metab Dispos 28:79–88.
  • David, S. P., Brown, R. A., Papandonatos, G. D., Kahler, C. W., Lloyd-Richardson, E. E., Munafo, M. R., Shields, P. G., Lerman, C., Strong, D., McCaffery, J. Niaura, R. (2007). Pharmacogenetic clinical trial of sustained-release bupropion for smoking cessation. Nicotine Tob Res 9:821–833.
  • Davies, B. J., Coller, J. K., Somogyi, A. A., Milne, R. W. Sallustio, B. C. (2007). CYP2B6, CYP2D6, and CYP3A4 catalyze the primary oxidative metabolism of perhexiline enantiomers by human liver microsomes. Drug Metab Dispos 35:128–138.
  • Davies, N. M. (1995). Clinical pharmacokinetics of flurbiprofen and its enantiomers. Clin Pharmacokinet 28:100–114.
  • Davies, N. M., McLachlan, A. J., Day, R. O. Williams, K. M. (2000). Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 38:225–242.
  • Davis, K. L., Thal, L. J., Gamzu, E. R., Davis, C. S., Woolson, R. F., Gracon, S. I., Drachman, D. A., Schneider, L. S., Whitehouse, P. J., Hoover, T. M. et al. (1992). A double-blind, placebo-controlled multicenter study of tacrine for Alzheimer’s disease. The Tacrine Collaborative Study Group. N Engl J Med 327:1253–1259.
  • Dayer, P., Gasser, R., Gut, J., Kronbach, T., Robertz, G. M., Eichelbaum, M. Meyer, U. A. (1984). Characterization of a common genetic defect of cytochrome P-450 function (debrisoquine-sparteine type polymorphism)—increased Michaelis Constant (Km) and loss of stereoselectivity of bufuralol 1’-hydroxylation in poor metabolizers. Biochem Biophys Res Commun 125:374–380.
  • Dayer, P., Leemann, T., Marmy, A. Rosenthaler, J. (1985). Interindividual variation of beta-adrenoceptor blocking drugs, plasma concentration and effect: influence of genetic status on behaviour of atenolol, bopindolol, and metoprolol. Eur J Clin Pharmacol 28:149–153.
  • Dayer, P., Leemann, T. Striberni, R. (1989). Dextromethorphan O-demethylation in liver microsomes as a prototype reaction to monitor cytochrome P-450 db1 activity. Clin Pharmacol Ther 45:34–40.
  • de Leon, J., Susce, M. T., Pan, R. M., Fairchild, M., Koch, W. H. Wedlund, P. J. (2005). The CYP2D6 poor metabolizer phenotype may be associated with risperidone adverse drug reactions and discontinuation. J Clin Psychiatry 66:15–27.
  • De Morais, S. M., Wilkinson, G. R., Blaisdell, J., Meyer, U. A., Nakamura, K. Goldstein, J. A. (1994a). Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. Mol Pharmacol 46:594–598.
  • de Morais, S. M., Wilkinson, G. R., Blaisdell, J., Nakamura, K., Meyer, U. A. Goldstein, J. A. (1994b). The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 269:15419–15422.
  • de Vos, J. W., Geerlings, P. J., van den Brink, W., Ufkes, J. G., van Wilgenburg, H. (1995). Pharmacokinetics of methadone and its primary metabolite in 20 opiate addicts. Eur J Clin Pharmacol 48:361–366.
  • de Waziers, I., Cugnenc, P. H., Yang, C. S., Leroux, J. P. Beaune, P. H. (1990). Cytochrome P 450 isoenzymes, epoxide hydrolase, and glutathione transferases in rat and human hepatic and extrahepatic tissues. J Pharmacol Exp Ther 253:387–394.
  • Dehal, S. S, Kupfer, D. (1994). Metabolism of the proestrogenic pesticide methoxychlor by hepatic P450 monooxygenases in rats and humans. Dual pathways involving novel ortho ring-hydroxylation by CYP2B. Drug Metab Dispos 22:937–946.
  • Dehal, S. S, Kupfer, D. (1996). Evidence that the catechol 3,4-dihydroxytamoxifen is a proximate intermediate to the reactive species binding covalently to proteins. Cancer Res 56:1283–1290.
  • Dehal, S. S, Kupfer, D. (1997). CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res 57:3402–3406.
  • Dehal, S. S, Kupfer, D. (1999). Cytochrome P-450 3A and 2D6 catalyze ortho hydroxylation of 4-hydroxytamoxifen and 3-hydroxytamoxifen (droloxifene) yielding tamoxifen catechol: involvement of catechols in covalent binding to hepatic proteins. Drug Metab Dispos 27:681–688.
  • Delaforge, M., Pruvost, A., Perrin, L. Andre, F. (2005). Cytochrome P450-mediated oxidation of glucuronide derivatives: example of estradiol-17beta-glucuronide oxidation to 2-hydroxy-estradiol-17beta-glucuronide by CYP 2C8. Drug Metab Dispos 33:466–473.
  • Delbressine, L. P., Moonen, M. E., Kaspersen, F. M., Wagenaars, G. N., Jacobs, P. L., Timmer, C. J., Paanakker, J. E., van Hal, H. J. Voortman, G. (1998). Pharmacokinetics and biotransformation of mirtazapine in human volunteers. Clin Drug Investig 15:45–55.
  • Dempsey, D., Tutka, P., Jacob, P., 3rd, Allen, F., Schoedel, K., Tyndale, R. F. Benowitz, N. L. (2004). Nicotine metabolite ratio as an index of cytochrome P450 2A6 metabolic activity. Clin Pharmacol Ther 76:64–72.
  • Desager, J. P. (1994). Clinical pharmacokinetics of ticlopidine. Clin Pharmacokinet 26:347–355.
  • Desta, Z., Saussele, T., Ward, B., Blievernicht, J., Li, L., Klein, K., Flockhart, D. A. Zanger, U. M. (2007). Impact of CYP2B6 polymorphism on hepatic efavirenz metabolism in vitro. Pharmacogenomics 8:547–558.
  • Desta, Z., Soukhova, N., Morocho, A. M. Flockhart, D. A. (2001). Stereoselective metabolism of cisapride and enantiomer-enantiomer interaction in human cytochrome P450 enzymes: major role of CYP3A. J Pharmacol Exp Ther 298:508–520.
  • Desta, Z., Ward, B. A., Soukhova, N. V. Flockhart, D. A. (2004). Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther 310:1062–1075.
  • Desta, Z., Wu, G. M., Morocho, A. M. Flockhart, D. A. (2002a). The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6. Drug Metab Dispos 30:336–343.
  • Desta, Z., Zhao, X., Shin, J. G. Flockhart, D. A. (2002b). Clinical significance of the cytochrome P450 2C19 genetic polymorphism. Clin Pharmacokinet 41:913–958.
  • Devonshire, H. W., Kong, I., Cooper, M., Sloan, T. P., Idle, J. R. Smith, R. L. (1983). The contribution of genetically determined oxidation status to interindividual variation in phenacetin disposition. Br J Clin Pharmacol 16:157–166.
  • Devore, N. M., Smith, B. D., Urban, M. J. Scott, E. E. (2008). Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes. Drug Metab Dispos doi: 10.1124/dmd.109.026765.
  • Dey, A., Parmar, D., Dayal, M., Dhawan, A. Seth, P. K. (2001). Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression. Life Sci 69:383–393.
  • Dhillon, S., Yang, L. P. Curran, M. P. (2008). Bupropion: a review of its use in the management of major depressive disorder. Drugs 68:653–689.
  • Dicke, K. E., Skrlin, S. M. Murphy, S. E. (2005). Nicotine and 4-(methylnitrosamino)-1-(3-pyridyl)-butanone metabolism by cytochrome P450 2B6. Drug Metab Dispos 33:1760–1764.
  • Dickmann, L. J., Rettie, A. E., Kneller, M. B., Kim, R. B., Wood, A. J., Stein, C. M., Wilkinson, G. R. Schwarz, U. I. (2001). Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans. Mol Pharmacol 60:382–387.
  • Diergaarde, B., Potter, J. D., Jupe, E. R., Manjeshwar, S., Shimasaki, C. D., Pugh, T. W., Defreese, D. C., Gramling, B. A., Evans, I. White, E. (2008). Polymorphisms in genes involved in sex hormone metabolism, estrogen plus progestin hormone therapy use, and risk of postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 17:1751–1759.
  • Dilger, K., Greiner, B., Fromm, M. F., Hofmann, U., Kroemer, H. K. Eichelbaum, M. (1999). Consequences of rifampicin treatment on propafenone disposition in extensive and poor metabolizers of CYP2D6. Pharmacogenetics 9:551–559.
  • Dilger, K., Hofmann, U. Klotz, U. (2000). Enzyme induction in the elderly: effect of rifampin on the pharmacokinetics and pharmacodynamics of propafenone. Clin Pharmacol Ther 67:512–520.
  • Ding, S., Lake, B. G., Friedberg, T. Wolf, C. R. (1995). Expression and alternative splicing of the cytochrome P-450 CYP2A7. Biochem J 306(Pt 1):161–166.
  • Dirven, H. A., Dictus, E. L., Broeders, N. L., van Ommen, B., van Bladeren, P. J. (1995). The role of human glutathione S-transferase isoenzymes in the formation of glutathione conjugates of the alkylating cytostatic drug thiotepa. Cancer Res 55:1701–1706.
  • Dixon, C. M., Colthup, P. V., Serabjit-Singh, C. J., Kerr, B. M., Boehlert, C. C., Park, G. R. Tarbit, M. H. (1995). Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 23:1225–1230.
  • Dojo, M., Azuma, T., Saito, T., Ohtani, M., Muramatsu, A. Kuriyama, M. (2001). Effects of CYP2C19 gene polymorphism on cure rates for Helicobacter pylori infection by triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin, and clarithromycin in Japan. Dig Liver Dis 33:671–675.
  • Doki, K., Homma, M., Kuga, K., Kusano, K., Watanabe, S., Yamaguchi, I. Kohda, Y. (2006). Effect of CYP2D6 genotype on flecainide pharmacokinetics in Japanese patients with supraventricular tachyarrhythmia. Eur J Clin Pharmacol 62:919–926.
  • Dorado, P., Berecz, R., Norberto, M. J., Yasar, U., Dahl, M. L. A, L. L. (2003). CYP2C9 genotypes and diclofenac metabolism in Spanish healthy volunteers. Eur J Clin Pharmacol 59:221–225.
  • Dorado, P., Berecz, R., Penas-Lledo, E. M., de la Rubia A., Llerena, A. (2007). No effect of the CYP1A2*1F genotype on thioridazine, mesoridazine, sulforidazine plasma concentrations in psychiatric patients. Eur J Clin Pharmacol 63:527–528.
  • Dowling, G. A., Mastick, J., Colling, E., Carter, J. H., Singer, C. M. Aminoff, M. J. (2005). Melatonin for sleep disturbances in Parkinson’s disease. Sleep Med 6:459–466.
  • Drakoulis, N., Cascorbi, I., Brockmoller, J., Gross, C. R. Roots, I. (1994). Polymorphisms in the human CYP1A1 gene as susceptibility factors for lung cancer: exon-7 mutation (4889 A to G), and a T to C mutation in the 3’-flanking region. Clin Investig 72:240–248.
  • Dreisbach, A. W., Japa, S., Sigel, A., Parenti, M. B., Hess, A. E., Srinouanprachanh, S. L., Rettie, A. E., Kim, H., Farin, F. M., Hamm, L. L. Lertora, J. J. (2005). The prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension. Am J Hypertens 18:1276–1281.
  • Dubocovich, M. L. Markowska, M. (2005). Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27:101–110.
  • Duescher, R. J. Elfarra, A. A. (1994). Human liver microsomes are efficient catalysts of 1,3-butadiene oxidation: evidence for major roles by cytochromes P450 2A6 and 2E1. Arch Biochem Biophys 311:342–349.
  • Dunn, C. J., Fitton, A. Brogden, R. N. (1995). Torasemide. An update of its pharmacological properties and therapeutic efficacy. Drugs 49:121–142.
  • Duran, D., Platia, E. V., Griffith, L. S., Adhar, G. Reid, P. R. (1982). Suppression of complex ventricular arrhythmias by oral flecainide. Clin Pharmacol Ther 32:554–561.
  • Eap, C. B., Bender, S., Gastpar, M., Fischer, W., Haarmann, C., Powell, K., Jonzier-Perey, M., Cochard, N. Baumann, P. (2000). Steady-state plasma levels of the enantiomers of trimipramine and of its metabolites in CYP2D6-, CYP2C19-, and CYP3A4/5-phenotyped patients. Ther Drug Monit 22:209–214.
  • Eap, C. B., Bender, S., Jaquenoud Sirot, E., Cucchia, G., Jonzier-Perey, M., Baumann, P., Allorge, D., Broly, F. (2004). Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. J Clin Psychopharmacol 24:214–219.
  • Eap, C. B., Bertschy, G., Powell, K. Baumann, P. (1997). Fluvoxamine and fluoxetine do not interact in the same way with the metabolism of the enantiomers of methadone. J Clin Psychopharmacol 17:113–117.
  • Eap, C. B., Guentert, T. W., Schaublin-Loidl, M., Stabl, M., Koeb, L., Powell, K. Baumann, P. (1996). Plasma levels of the enantiomers of thioridazine, thioridazine 2-sulfoxide, thioridazine 2-sulfone, and thioridazine 5-sulfoxide in poor and extensive metabolizers of dextromethorphan and mephenytoin. Clin Pharmacol Ther 59:322–331.
  • Eap, C. B., Lessard, E., Baumann, P., Brawand-Amey, M., Yessine, M. A., O’Hara, G. Turgeon, J. (2003). Role of CYP2D6 in the stereoselective disposition of venlafaxine in humans. Pharmacogenetics 13:39–47.
  • Eaton, D. L., Gallagher, E. P., Bammler, T. K. Kunze, K. L. (1995). Role of cytochrome P4501A2 in chemical carcinogenesis: implications for human variability in expression and enzyme activity. Pharmacogenetics 5:259–274.
  • Ebert, B., Thorkildsen, C., Andersen, S., Christrup, L. L. Hjeds, H. (1998). Opioid analgesics as noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Biochem Pharmacol 56:553–559.
  • Ebisawa, A., Hiratsuka, M., Sakuyama, K., Konno, Y., Sasaki, T. Mizugaki, M. (2005). Two novel single-nucleotide polymorphisms (SNPs) of the CYP2D6 gene in Japanese individuals. Drug Metab Pharmacokinet 20:294–299.
  • Ebner, T. Burchell, B. (1993). Substrate specificities of two stably expressed human liver UDP-glucuronosyltransferases of the UGT1 gene family. Drug Metab Dispos 21:50–55.
  • Ebner, T. Eichelbaum, M. (1993). The metabolism of aprindine in relation to the sparteine/debrisoquine polymorphism. Br J Clin Pharmacol 35:426–430.
  • Ebner, T., Meese, C. O. Eichelbaum, M. (1995). Mechanism of cytochrome P450 2D6-catalyzed sparteine metabolism in humans. Mol Pharmacol 48:1078–1086.
  • Eckhardt, K., Li, S., Ammon, S., Schanzle, G., Mikus, G. Eichelbaum, M. (1998). Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation. Pain 76:27–33.
  • Edstein, M. D., Yeo, A. E., Kyle, D. E., Looareesuwan, S., Wilairatana, P. Rieckmann, K. H. (1996). Proguanil polymorphism does not affect the antimalarial activity of proguanil combined with atovaquone in vitro. Trans R Soc Trop Med Hyg 90:418–421.
  • Edwards, S. J., Lind, T. Lundell, L. (2006). Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis—a comparison of esomeprazole with other PPIs. Aliment Pharmacol Ther 24:743–750.
  • Egan, L. J., Myhre, G. M., Mays, D. C., Dierkhising, R. A., Kammer, P. P. Murray, J. A. (2003). CYP2C19 pharmacogenetics in the clinical use of proton-pump inhibitors for gastro-oesophageal reflux disease: variant alleles predict gastric acid suppression, but not oesophageal acid exposure or reflux symptoms. Aliment Pharmacol Ther 17:1521–1528.
  • Eichelbaum, M., Baur, M. P., Dengler, H. J., Osikowska-Evers, B. O., Tieves, G., Zekorn, C. Rittner, C. (1987). Chromosomal assignment of human cytochrome P-450 (debrisoquine/sparteine type) to chromosome 22. Br J Clin Pharmacol 23:455–458.
  • Eichelbaum, M., Mineshita, S., Ohnhaus, E. E. Zekorn, C. (1986a). The influence of enzyme induction on polymorphic sparteine oxidation. Br J Clin Pharmacol 22:49–53.
  • Eichelbaum, M., Reetz, K. P., Schmidt, E. K. Zekorn, C. (1986b). The genetic polymorphism of sparteine metabolism. Xenobiotica 16:465–481.
  • Eichelbaum, M., Spannbrucker, N. Dengler, H. J. (1975). Proceedings: N-oxidation of sparteine in man and its interindividual differences. Naunyn Schmiedebergs Arch Pharmacol 287 (Suppl): R94.
  • Eichelbaum, M., Spannbrucker, N. Dengler, H. J. (1979a). Influence of the defective metabolism of sparteine on its pharmacokinetics. Eur J Clin Pharmacol 16:189–194.
  • Eichelbaum, M., Spannbrucker, N., Steincke, B. Dengler, H. J. (1979b). Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. Eur J Clin Pharmacol 16:183–187.
  • Eiermann, B., Edlund, P. O., Tjernberg, A., Dalen, P., Dahl, M. L. Bertilsson, L. (1998). 1- and 3-hydroxylations, in addition to 4-hydroxylation, of debrisoquine are catalyzed by cytochrome P450 2D6 in humans. Drug Metab Dispos 26:1096–1101.
  • Eiermann, B., Engel, G., Johansson, I., Zanger, U. M. Bertilsson, L. (1997). The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 44:439–446.
  • Eiselt, R., Domanski, T. L., Zibat, A., Mueller, R., Presecan-Siedel, E., Hustert, E., Zanger, U. M., Brockmoller, J., Klenk, H. P., Meyer, U. A., Khan, K. K., He, Y. A., Halpert, J. R. Wojnowski, L. (2001). Identification and functional characterization of eight CYP3A4 protein variants. Pharmacogenetics 11:447–458.
  • Ekhart, C., Doodeman, V. D., Rodenhuis, S., Smits, P. H., Beijnen, J. H. Huitema, A. D. (2008). Influence of polymorphisms of drug metabolizing enzymes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1, and ALDH3A1) on the pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide. Pharmacogenet Genomics 18:515–523.
  • Ekhart, C., Doodeman, V. D., Rodenhuis, S., Smits, P. H., Beijnen, J. H. Huitema, A. D. (2009). Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6, and CYP3A) affect the pharmacokinetics of thiotepa and tepa. Br J Clin Pharmacol 67:50–60.
  • Ekins, S., Vandenbranden, M., Ring, B. J., Gillespie, J. S., Yang, T. J., Gelboin, H. V. Wrighton, S. A. (1998). Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther 286:1253–1259.
  • Ellingrod, V. L. Perry, P. J. (1994). Venlafaxine: a heterocyclic antidepressant. Am J Hosp Pharm 51:3033–3046.
  • Emborg, M. E. (2007). Nonhuman primate models of Parkinson’s disease. Ilar J 48:339–355.
  • Emoto, C. Iwasaki, K. (2007). Relative roles of CYP2C19 and CYP3A4/5 in midazolam 1’-hydroxylation. Xenobiotica 37:592–603.
  • Endo, T., Ban, M., Hirata, K., Yamamoto, A., Hara, Y. Momose, Y. (2007). Involvement of CYP2A6 in the formation of a novel metabolite, 3-hydroxypilocarpine, from pilocarpine in human liver microsomes. Drug Metab Dispos 35:476–483.
  • Endo, T., Nakajima, M., Fukami, T., Hara, Y., Hasunuma, T., Yokoi, T. Momose, Y. (2008). Genetic polymorphisms of CYP2A6 affect the in-vivo pharmacokinetics of pilocarpine. Pharmacogenet Genomics 18:761–772.
  • Enggaard, T. P., Poulsen, L., Arendt-Nielsen, L., Brosen, K., Ossig, J. Sindrup, S. H. (2006). The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6. Anesth Analg 102:146–150.
  • Erickson, D. A., Mather, G., Trager, W. F., Levy, R. H. Keirns, J. J. (1999). Characterization of the in vitro biotransformation of the HIV-1 reverse transcriptase inhibitor nevirapine by human hepatic cytochromes P-450. Drug Metab Dispos 27:1488–1495.
  • Erkinjuntti, T., Gauthier, S., Bullock, R., Kurz, A., Hammond, G., Schwalen, S., Zhu, Y. Brashear, R. (2008). Galantamine treatment in Alzheimer’s disease with cerebrovascular disease: responder analyses from a randomized, controlled trial (GAL-INT-6). J Psychopharmacol 22:761–768.
  • Erkinjuntti, T., Kurz, A., Gauthier, S., Bullock, R., Lilienfeld, S. Damaraju, C. V. (2002). Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial. Lancet 359:1283–1290.
  • Etienne, M. C., Milano, G., Fischel, J. L., Frenay, M., Francois, E., Formento, J. L., Gioanni, J. Namer, M. (1989). Tamoxifen metabolism: pharmacokinetic and in vitro study. Br J Cancer 60:30–35.
  • Eugster, H. P., Probst, M., Wurgler, F. E. Sengstag, C. (1993). Caffeine, estradiol, and progesterone interact with human CYP1A1 and CYP1A2. Evidence from cDNA-directed expression in Saccharomyces cerevisiae. Drug Metab Dispos 21:3–49.
  • Evangelista, S. (2001). Eziopitant. Pfizer. Curr Opin Investig Drugs 2:1441–1443.
  • Evans, W. E. Relling, M. V. (1999). Pharmacogenomics: translating functional genomics into rational therapeutics. Science 286:487–491.
  • Evans, W. E., Relling, M. V., Petros, W. P., Meyer, W. H., Mirro, J., Jr., Crom, W. R. (1989). Dextromethorphan and caffeine as probes for simultaneous determination of debrisoquin-oxidation and N-acetylation phenotypes in children. Clin Pharmacol Ther 45:568–573.
  • Evert, B., Griese, E. U. Eichelbaum, M. (1994a). Cloning and sequencing of a new nonfunctional CYP2D6 allele: deletion of T1795 in exon 3 generates a premature stop codon. Pharmacogenetics 4:271–274.
  • Evert, B., Griese, E. U. Eichelbaum, M. (1994b). A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine 324 to proline exchange is associated with the poor metabolizer phenotype of sparteine. Naunyn Schmiedebergs Arch Pharmacol 350:434–439.
  • Fabre, G., Julian, B., Saint-Aubert, B., Joyeux, H. Berger, Y. (1993). Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab Dispos 21:978–985.
  • Facciola, G., Hidestrand, M., von Bahr, C., Tybring, G. (2001). Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. Eur J Clin Pharmacol 56:881–888.
  • Falany, J. L., Pilloff, D. E., Leyh, T. S. Falany, C. N. (2006). Sulfation of raloxifene and 4-hydroxytamoxifen by human cytosolic sulfotransferases. Drug Metab Dispos 34:361–368.
  • Falk, R. H. Fogel, R. I. (1994). Flecainide. J Cardiovasc Electrophysiol 5:964–981.
  • Fan, P. W. Bolton, J. L. (2001). Bioactivation of tamoxifen to metabolite E quinone methide: reaction with glutathione and DNA. Drug Metab Dispos 29:891–896.
  • Fan, P. W., Zhang, F. Bolton, J. L. (2000). 4-Hydroxylated metabolites of the antiestrogens tamoxifen and toremifene are metabolized to unusually stable quinone methides. Chem Res Toxicol 13:45–52.
  • Fang, J., Coutts, R. T., McKenna, K. F. Baker, G. B. (1998). Elucidation of individual cytochrome P450 enzymes involved in the metabolism of clozapine. Naunyn Schmiedebergs Arch Pharmacol 358:592–599.
  • Fang, J., McKay, G., Song, J., Remillrd, A., Li, X. Midha, K. (2001). In vitro characterization of the metabolism of haloperidol using recombinant cytochrome p450 enzymes and human liver microsomes. Drug Metab Dispos 29:1638–1643.
  • Fargion, S., Fracanzani, A. L., Romano, R., Cappellini, M. D., Fare, M., Mattioli, M., Piperno, A., Ronchi, G. Fiorelli, G. (1996). Genetic hemochromatosis in Italian patients with porphyria cutanea tarda: possible explanation for iron overload. J Hepatol 24:564–569.
  • Farid, N. A., Bergstrom, R. F., Ziege, E. A., Parli, C. J. Lemberger, L. (1985). Single-dose and steady-state pharmacokinetics of tomoxetine in normal subjects. J Clin Pharmacol 25:296–301.
  • Farid, N. A., Payne, C. D., Ernest, C. S., 2nd, Li, Y. G., Winters, K. J., Salazar, D. E. Small, D. S. (2008). Prasugrel, a new thienopyridine antiplatelet drug, weakly inhibits cytochrome P450 2B6 in humans. J Clin Pharmacol 48:53–59.
  • Farid, N. A., Smith, R. L., Gillespie, T. A., Rash, T. J., Blair, P. E., Kurihara, A. Goldberg, M. J. (2007). The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos 35:1096–1104.
  • Farinola, N. Piller, N. B. (2007). CYP2A6 polymorphisms: is there a role for pharmacogenomics in preventing coumarin-induced hepatotoxicity in lymphedema patients? Pharmacogenomics 8:151–158.
  • Farlow, M., Gracon, S. I., Hershey, L. A., Lewis, K. W., Sadowsky, C. H. Dolan-Ureno, J. (1992). A controlled trial of tacrine in Alzheimer’s disease. The Tacrine Study Group. JAMA 268:2523–2529.
  • Fasola, A. F. Carmichael, R. (1974). The pharmacology and clinical evaluation of aprindine a new antiarrhythmic agent. Acta Cardiol Suppl 18:317–333.
  • Faucette, S. R., Hawke, R. L., Lecluyse, E. L., Shord, S. S., Yan, B., Laethem, R. M. Lindley, C. M. (2000). Validation of bupropion hydroxylation as a selective marker of human cytochrome P450 2B6 catalytic activity. Drug Metab Dispos 28:1222–1230.
  • Faucette, S. R., Wang, H., Hamilton, G. A., Jolley, S. L., Gilbert, D., Lindley, C., Yan, B., Negishi, M. LeCluyse, E. L. (2004). Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos 32:348–358.
  • Faucette, S. R., Zhang, T. C., Moore, R., Sueyoshi, T., Omiecinski, C. J., LeCluyse, E. L., Negishi, M. Wang, H. (2007). Relative activation of human pregnane X receptor versus constitutive androstane receptor defines distinct classes of CYP2B6 and CYP3A4 inducers. J Pharmacol Exp Ther 320:72–80.
  • Favetta, P., Degoute, C. S., Perdrix, J. P., Dufresne, C., Boulieu, R. Guitton, J. (2002). Propofol metabolites in man following propofol induction and maintenance. Br J Anaesth 88:653–658.
  • Favetta, P., Dufresne, C., Desage, M., Paisse, O., Perdrix, J. P., Boulieu, R. Guitton, J. (2000a). Detection of new propofol metabolites in human urine using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry techniques. Rapid Commun Mass Spectrom 14:1932–1936.
  • Favetta, P., Guitton, J., Degoute, C. S., Van Daele, L., Boulieu, R. (2000b). High-performance liquid chromatographic assay to detect hydroxylate and conjugate metabolites of propofol in human urine. J Chromatogr B Biomed Sci Appl 742:25–35.
  • Felix, C. A., Walker, A. H., Lange, B. J., Williams, T. M., Winick, N. J., Cheung, N. K., Lovett, B. D., Nowell, P. C., Blair, I. A. Rebbeck, T. R. (1998). Association of CYP3A4 genotype with treatment-related leukemia. Proc Natl Acad Sci USA 95:13176–13181.
  • Felsher, B. F., Norris, M. E. Shih, J. C. (1978). Red-cell uroporphyrinogen decarboxylase activity in porphyria cutanea tarda and in other forms of porphyria. N Engl J Med 299:1095–1098.
  • Fenselau, C., Kan, M. N., Rao, S. S., Myles, A., Friedman, O. M. Colvin, M. (1977). Identification of aldophosphamide as a metabolite of cyclophosphamide in vitro and in vivo in humans. Cancer Res 37:2538–2543.
  • Fenton, M., Rathbone, J., Reilly, J. Sultana, A. (2007). Thioridazine for schizophrenia. Cochrane Database Syst Rev CD001944.
  • Ferguson, R. J., De Morais, S. M., Benhamou, S., Bouchardy, C., Blaisdell, J., Ibeanu, G., Wilkinson, G. R., Sarich, T. C., Wright, J. M., Dayer, P. Goldstein, J. A. (1998). A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. J Pharmacol Exp Ther 284:356–361.
  • Fernandez-Salguero, P. Gonzalez, F. J. (1995). The CYP2A gene subfamily: species differences, regulation, catalytic activities, and role in chemical carcinogenesis. Pharmacogenetics 5 Spec No:S123–S128.
  • Fernandez-Salguero, P., Hoffman, S. M., Cholerton, S., Mohrenweiser, H., Raunio, H., Rautio, A., Pelkonen, O., Huang, J. D., Evans, W. E., Idle, J. R. et al. (1995). A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. Am J Hum Genet 57:651–660.
  • Finta, C. Zaphiropoulos, P. G. (2000). The human cytochrome P450 3A locus. Gene evolution by capture of downstream exons. Gene 260:13–23.
  • Fioravanti, M. Flicker, L. (2001). Efficacy of nicergoline in dementia and other age associated forms of cognitive impairment. Cochrane Database Syst Rev CD003159.
  • Fiorella, D., Rabin, R. A. Winter, J. C. (1995). The role of the 5-HT2A and 5-HT2C receptors in the stimulus effects of m-chlorophenylpiperazine. Psychopharmacology (Berl) 119:222–230.
  • Firkusny, L. Gleiter, C. H. (1994). Maprotiline metabolism appears to cosegregate with the genetically-determined CYP2D6 polymorphic hydroxylation of debrisoquine. Br J Clin Pharmacol 37:383–388.
  • Firkusny, L., Kroemer, H. K. Eichelbaum, M. (1995). In vitro characterization of cytochrome P450 catalysed metabolism of the antiemetic tropisetron. Biochem Pharmacol 49:1777–1784.
  • Fischer, D. Breyer-Pfaff, U. (1997). Variability of diphenhydramine N-glucuronidation in healthy subjects. Eur J Drug Metab Pharmacokinet 22:151–154.
  • Fischer, T. L., Pieper, J. A., Graff, D. W., Rodgers, J. E., Fischer, J. D., Parnell, K. J., Goldstein, J. A., Greenwood, R. Patterson, J. H. (2002). Evaluation of potential losartan-phenytoin drug interactions in healthy volunteers. Clin Pharmacol Ther 72:238–246.
  • Fischer, V., Baldeck, J. P. Tse, F. L. (1992a). Pharmacokinetics and metabolism of the 5-hydroxytryptamine antagonist tropisetron after single oral doses in humans. Drug Metab Dispos 20:603–607.
  • Fischer, V., Johanson, L., Heitz, F., Tullman, R., Graham, E., Baldeck, J. P. Robinson, W. T. (1999). The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor fluvastatin: effect on human cytochrome P-450 and implications for metabolic drug interactions. Drug Metab Dispos 27:410–416.
  • Fischer, V., Vickers, A. E., Heitz, F., Mahadevan, S., Baldeck, J. P., Minery, P. Tynes, R. (1994). The polymorphic cytochrome P-4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron. Drug Metab Dispos 22:269–274.
  • Fischer, V., Vogels, B., Maurer, G. Tynes, R. E. (1992b). The antipsychotic clozapine is metabolized by the polymorphic human microsomal and recombinant cytochrome P450 2D6. J Pharmacol Exp Ther 260:1355–1360.
  • Fisslthaler, B., Popp, R., Kiss, L., Potente, M., Harder, D. R., Fleming, I. Busse, R. (1999). Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 401:493–497.
  • Fjordside, L., Jeppesen, U., Eap, C. B., Powell, K., Baumann, P. Brosen, K. (1999). The stereoselective metabolism of fluoxetine in poor and extensive metabolizers of sparteine. Pharmacogenetics 9:55–60.
  • Flanagan, J. U., Marechal, J. D., Ward, R., Kemp, C. A., McLaughlin, L. A., Sutcliffe, M. J., Roberts, G. C., Paine, M. J. Wolf, C. R. (2004). Phe120 contributes to the regiospecificity of cytochrome P450 2D6: mutation leads to the formation of a novel dextromethorphan metabolite. Biochem J 380:353–360.
  • Fliegert, F., Kurth, B. Gohler, K. (2005). The effects of tramadol on static and dynamic pupillometry in healthy subjects—the relationship between pharmacodynamics, pharmacokinetics, and CYP2D6 metaboliser status. Eur J Clin Pharmacol 61:257–266.
  • Flockhart, D. A., O’Kane, D., Williams, M. S., Watson, M. S., Flockhart, D. A., Gage, B., Gandolfi, R., King, R., Lyon, E., Nussbaum, R., O’Kane, D., Schulman, K., Veenstra, D., Williams, M. S. Watson, M. S. (2008). Pharmacogenetic testing of CYP2C9 and VKORC1 alleles for warfarin. Genet Med 10:139–150.
  • Flores-Runk, P. Raasch, R. H. (1993). Ticlopidine and antiplatelet therapy. Ann Pharmacother 27:1090–1098.
  • Fogelman, S. M., Schmider, J., Venkatakrishnan, K., von Moltke, L. L., Harmatz, J. S., Shader, R. I. Greenblatt, D. J. (1999). O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology 20:480–490.
  • Foglia, J. P., Pollock, B. G., Kirshner, M. A., Rosen, J., Sweet, R. Mulsant, B. (1997). Plasma levels of citalopram enantiomers and metabolites in elderly patients. Psychopharmacol Bull 33:109–112.
  • Follath, F. (1992). The utility of serum drug level monitoring during therapy with class III antiarrhythmic agents. J Cardiovasc Pharmacol 20(Suppl 2):S41–S43.
  • Forland, S. C., Cutler, R. E., McQuinn, R. L., Kvam, D. C., Miller, A. M., Conard, G. J. Parish, S. (1988). Flecainide pharmacokinetics after multiple dosing in patients with impaired renal function. J Clin Pharmacol 28:727–735.
  • Forsyth, D. R., Wilcock, G. K., Morgan, R. A., Truman, C. A., Ford, J. M. Roberts, C. J. (1989). Pharmacokinetics of tacrine hydrochloride in Alzheimer’s disease. Clin Pharmacol Ther 46:634–641.
  • Foster, A. B., Griggs, L. J., Jarman, M., van Maanen, J. M. Schulten, H. R. (1980). Metabolism of tamoxifen by rat liver microsomes: formation of the N-oxide, a new metabolite. Biochem Pharmacol 29:1977–1979.
  • Foster, D. J., Somogyi, A. A. Bochner, F. (1999). Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4. Br J Clin Pharmacol 47:403–412.
  • Fox, S. H., Koepsell, T. D. Daling, J. R. (1994). Birth weight and smoking during pregnancy—effect modification by maternal age. Am J Epidemiol 139:1008–1015.
  • Freimuth, W. W. (1996). Delavirdine mesylate, a potent non-nucleoside HIV-1 reverse transcriptase inhibitor. Adv Exp Med Biol 394: 279–289.
  • Frelinger, A. L., 3rd, Jakubowski, J. A., Li, Y., Barnard, M. R., Linden, M. D., Tarnow, I., Fox, M. L., Sugidachi, A., Winters, K. J., Furman, M. I. Michelson, A. D. (2008). The active metabolite of prasugrel inhibits adenosine diphosphate- and collagen-stimulated platelet procoagulant activities. J Thromb Haemost 6:359–365.
  • Fried, K. M. Wainer, I. W. (1994). Direct determination of tamoxifen and its four major metabolites in plasma using coupled column high-performance liquid chromatography. J Chromatogr B Biomed Appl 655:261–268.
  • Fritz, S., Lindner, W., Roots, I., Frey, B. M. Kupfer, A. (1987). Stereochemistry of aromatic phenytoin hydroxylation in various drug hydroxylation phenotypes in humans. J Pharmacol Exp Ther 241:615–622.
  • Fromm, M. F., Hofmann, U., Griese, E. U. Mikus, G. (1995). Dihydrocodeine: a new opioid substrate for the polymorphic CYP2D6 in humans. Clin Pharmacol Ther 58:374–382.
  • Fuhr, U., Kober, S., Zaigler, M., Mutschler, E. Spahn-Langguth, H. (2005). Rate-limiting biotransformation of triamterene is mediated by CYP1A2. Int J Clin Pharmacol Ther 43:327–334.
  • Fujieda, M., Yamazaki, H., Kiyotani, K., Muroi, A., Kunitoh, H., Dosaka-Akita, H., Sawamura, Y. Kamataki, T. (2003). Eighteen novel polymorphisms of the CYP2A13 gene in Japanese. Drug Metab Pharmacokinet 18:86–90.
  • Fujieda, M., Yamazaki, H., Saito, T., Kiyotani, K., Gyamfi, M. A., Sakurai, M., Dosaka-Akita, H., Sawamura, Y., Yokota, J., Kunitoh, H. Kamataki, T. (2004). Evaluation of CYP2A6 genetic polymorphisms as determinants of smoking behavior and tobacco-related lung cancer risk in male Japanese smokers. Carcinogenesis 25:2451–2458.
  • Fujimura, H., Tsurumi, K., Yanagihara, M., Hiramatsu, Y., Tamura, Y., Shimizu, Y., Hojo, M., Yoshida, Y. Akimoto, Y. (1981). [Pharmacological study of mequitazine (LM-209) (II). Anti-allergic action (author’s transl)]. Nippon Yakurigaku Zasshi 78:291–303.
  • Fujita, K., Yamamoto, W., Endo, S., Endo, H., Nagashima, F., Ichikawa, W., Tanaka, R., Miya, T., Araki, K., Kodama, K., Sunakawa, Y., Narabayashi, M., Miwa, K., Ando, Y., Akiyama, Y., Kawara, K., Kamataki, T. Sasaki, Y. (2008). CYP2A6 and the plasma level of 5-chloro-2,4-dihydroxypyridine are determinants of the pharmacokinetic variability of tegafur and 5-fluorouracil, respectively, in Japanese patients with cancer given S-1. Cancer Sci 99:1049–1054.
  • Fukami, T., Nakajima, M., Higashi, E., Yamanaka, H., McLeod, H. L. Yokoi, T. (2005a). A novel CYP2A6*20 allele found in African-American population produces a truncated protein lacking enzymatic activity. Biochem Pharmacol 70:801–808.
  • Fukami, T., Nakajima, M., Higashi, E., Yamanaka, H., Sakai, H., McLeod, H. L. Yokoi, T. (2005b). Characterization of novel CYP2A6 polymorphic alleles (CYP2A6*18 and CYP2A6*19) that affect enzymatic activity. Drug Metab Dispos 33:1202–1210.
  • Fukami, T., Nakajima, M., Sakai, H., Katoh, M. Yokoi, T. (2007a). CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline. Drug Metab Dispos 35:335–339.
  • Fukami, T., Nakajima, M., Yamanaka, H., Fukushima, Y., McLeod, H. L. Yokoi, T. (2007b). A novel duplication type of CYP2A6 gene in African-American population. Drug Metab Dispos 35:515–520.
  • Fukami, T., Nakajima, M., Yoshida, R., Tsuchiya, Y., Fujiki, Y., Katoh, M., McLeod, H. L. Yokoi, T. (2004). A novel polymorphism of human CYP2A6 gene CYP2A6*17 has an amino acid substitution (V365M) that decreases enzymatic activity in vitro and in vivo. Clin Pharmacol Ther 76:519–527.
  • Fukasawa, T., Yasui-Furukori, N., Aoshima, T., Suzuki, A., Tateishi, T. Otani, K. (2004). Single oral dose pharmacokinetics of quazepam is influenced by CYP2C19 activity. Ther Drug Monit 26:529–533.
  • Fukuda, T., Nishida, Y., Imaoka, S., Hiroi, T., Naohara, M., Funae, Y. Azuma, J. (2000a). The decreased in vivo clearance of CYP2D6 substrates by CYP2D6*10 might be caused not only by the low-expression but also by low affinity of CYP2D6. Arch Biochem Biophys 380:303–308.
  • Fukuda, T., Nishida, Y., Zhou, Q., Yamamoto, I., Kondo, S. Azuma, J. (2000b). The impact of the CYP2D6 and CYP2C19 genotypes on venlafaxine pharmacokinetics in a Japanese population. Eur J Clin Pharmacol 56:175–180.
  • Fukuen, S., Fukuda, T., Matsuda, H., Sumida, A., Yamamoto, I., Inaba, T. Azuma, J. (2002a). Identification of the novel splicing variants for the hPXR in human livers. Biochem Biophys Res Commun 298:433–438.
  • Fukuen, S., Fukuda, T., Maune, H., Ikenaga, Y., Yamamoto, I., Inaba, T. Azuma, J. (2002b). Novel detection assay by PCR-RFLP and frequency of the CYP3A5 SNPs, CYP3A5*3 and *6, in a Japanese population. Pharmacogenetics 12:331–334.
  • Fukushima-Uesaka, H., Saito, Y., Maekawa, K., Ozawa, S., Hasegawa, R., Kajio, H., Kuzuya, N., Yasuda, K., Kawamoto, M., Kamatani, N., Suzuki, K., Yanagawa, T., Tohkin, M. Sawada, J. (2005). Genetic variations and haplotypes of CYP2C19 in a Japanese population. Drug Metab Pharmacokinet 20:300–307.
  • Fukushima-Uesaka, H., Saito, Y., Watanabe, H., Shiseki, K., Saeki, M., Nakamura, T., Kurose, K., Sai, K., Komamura, K., Ueno, K., Kamakura, S., Kitakaze, M., Hanai, S., Nakajima, T., Matsumoto, K., Saito, H., Goto, Y., Kimura, H., Katoh, M., Sugai, K., Minami, N., Shirao, K., Tamura, T., Yamamoto, N., Minami, H., Ohtsu, A., Yoshida, T., Saijo, N., Kitamura, Y., Kamatani, N., Ozawa, S. Sawada, J. (2004). Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population. Hum Mutat 23:100.
  • Fukuuchi, Y., Tohgi, H., Okudera, T., Ikeda, Y., Miyanaga, Y., Uchiyama, S., Hirano, M., Shinohara, Y., Matsumoto, M. Yamaguchi, T. (2008). A randomized, double-blind study comparing the safety and efficacy of clopidogrel versus ticlopidine in Japanese patients with noncardioembolic cerebral infarction. Cerebrovasc Dis 25:40–49.
  • Fulton, B. Sorkin, E. M. (1995). Propofol. An overview of its pharmacology and a review of its clinical efficacy in intensive care sedation. Drugs 50:636–657.
  • Funch-Brentano, C., Becquemont, L., Kroemer, K. H., Kerstin, B., Knebel, N. G., Eichelbaum, M. Jaillon, P. (1994). Variable disposition kinetics and electrocardiographic effects of flecainide during repeated dosing in humans: contribution of genetic factors, dose-dependent clearance, and interaction with amiodarone. Clin Pharmacol Ther 55:256–269.
  • Funck-Brentano, C., Becquemont, L., Lenevu, A., Roux, A., Jaillon, P. Beaune, P. (1997). Inhibition by omeprazole of proguanil metabolism: mechanism of the interaction in vitro and prediction of in vivo results from the in vitro experiments. J Pharmacol Exp Ther 280:730–738.
  • Funck-Brentano, C., Bosco, O., Jacqz-Aigrain, E., Keundjian, A. Jaillon, P. (1992a). Relation between chloroguanide bioactivation to cycloguanil and the genetically determined metabolism of mephenytoin in humans. Clin Pharmacol Ther 51:507–512.
  • Funck-Brentano, C., Thomas, G., Jacqz-Aigrain, E., Poirier, J. M., Simon, T., Bereziat, G. Jaillon, P. (1992b). Polymorphism of dextromethorphan metabolism: relationships between phenotype, genotype, and response to the administration of encainide in humans. J Pharmacol Exp Ther 263:780–786.
  • Furuno, T., Kawanishi, C., Iseki, E., Onishi, H., Sugiyama, N., Suzuki, K. Kosaka, K. (2001). No evidence of an association between CYP2D6 polymorphisms among Japanese and dementia with Lewy bodies. Psychiatry Clin Neurosci 55:89–92.
  • Furuta, T., Ohashi, K., Kobayashi, K., Iida, I., Yoshida, H., Shirai, N., Takashima, M., Kosuge, K., Hanai, H., Chiba, K., Ishizaki, T. Kaneko, E. (1999a). Effects of clarithromycin on the metabolism of omeprazole in relation to CYP2C19 genotype status in humans. Clin Pharmacol Ther 66:265–274.
  • Furuta, T., Ohashi, K., Kosuge, K., Zhao, X. J., Takashima, M., Kimura, M., Nishimoto, M., Hanai, H., Kaneko, E. Ishizaki, T. (1999b). CYP2C19 genotype status and effect of omeprazole on intragastric pH in humans. Clin Pharmacol Ther 65:552–561.
  • Furuta, T., Shirai, N., Takashima, M., Xiao, F., Hanai, H., Nakagawa, K., Sugimura, H., Ohashi, K. Ishizaki, T. (2001a). Effects of genotypic differences in CYP2C19 status on cure rates for Helicobacter pylori infection by dual therapy with rabeprazole plus amoxicillin. Pharmacogenetics 11:341–348.
  • Furuta, T., Shirai, N., Takashima, M., Xiao, F., Hanai, H., Sugimura, H., Ohashi, K., Ishizaki, T. Kaneko, E. (2001b). Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Clin Pharmacol Ther 69:158–168.
  • Furuta, T., Shirai, N., Watanabe, F., Honda, S., Takeuchi, K., Iida, T., Sato, Y., Kajimura, M., Futami, H., Takayanagi, S., Yamada, M., Ohashi, K., Ishizaki, T. Hanai, H. (2002). Effect of cytochrome P4502C19 genotypic differences on cure rates for gastroesophageal reflux disease by lansoprazole. Clin Pharmacol Ther 72:453–460.
  • Furuta, T., Shirai, N., Xiao, F., Ohashi, K. Ishizaki, T. (2001c). Effect of high-dose lansoprazole on intragastic pH in subjects who are homozygous extensive metabolizers of cytochrome P4502C19. Clin Pharmacol Ther 70:484–492.
  • Furuta, T., Sugimoto, M., Shirai, N. Ishizaki, T. (2007). CYP2C19 pharmacogenomics associated with therapy of Helicobacter pylori infection and gastro-esophageal reflux diseases with a proton pump inhibitor. Pharmacogenomics 8:1199–1210.
  • Fuselli, S., Dupanloup, I., Frigato, E., Cruciani, F., Scozzari, R., Moral, P., Sistonen, J., Sajantila, A. Barbujani, G. (2004). Molecular diversity at the CYP2D6 locus in the Mediterranean region. Eur J Hum Genet 12:916–924.
  • Fux, R., Morike, K., Prohmer, A. M., Delabar, U., Schwab, M., Schaeffeler, E., Lorenz, G., Gleiter, C. H., Eichelbaum, M. Kivisto, K. T. (2005). Impact of CYP2D6 genotype on adverse effects during treatment with metoprolol: a prospective, clinical study. Clin Pharmacol Ther 78:378–387.
  • Gaedigk, A., Bhathena, A., Ndjountche, L., Pearce, R. E., Abdel-Rahman, S. M., Alander, S. W., Bradford, L. D., Rogan, P. K. Leeder, J. S. (2005a). Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans. Pharmacogenomics J 5:173–182.
  • Gaedigk, A., Blum, M., Gaedigk, R., Eichelbaum, M. Meyer, U. A. (1991). Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet 48:943–950.
  • Gaedigk, A., Bradford, L. D., Alander, S. W. Leeder, J. S. (2006). CYP2D6*36 gene arrangements within the cyp2d6 locus: association of CYP2D6*36 with poor metabolizer status. Drug Metab Dispos 34:563–569.
  • Gaedigk, A., Bradford, L. D., Marcucci, K. A. Leeder, J. S. (2002). Unique CYP2D6 activity distribution and genotype-phenotype discordance in black Americans. Clin Pharmacol Ther 72:76–89.
  • Gaedigk, A., Casley, W. L., Tyndale, R. F., Sellers, E. M., Jurima-Romet, M. Leeder, J. S. (2001). Cytochrome P4502C9 (CYP2C9) allele frequencies in Canadian Native Indian and Inuit populations. Can J Physiol Pharmacol 79:841–847.
  • Gaedigk, A. Coetsee, C. (2008). The CYP2D6 gene locus in South African Coloureds: unique allele distributions, novel alleles, and gene arrangements. Eur J Clin Pharmacol 64:465–475.
  • Gaedigk, A., Eklund, J. D., Pearce, R. E., Leeder, J. S., Alander, S. W., Phillips, M. S., Bradford, L. D. Kennedy, M. J. (2007a). Identification and characterization of CYP2D6*56B, an allele associated with the poor metabolizer phenotype. Clin Pharmacol Ther 81:817–820.
  • Gaedigk, A., Frank, D. Fuhr, U. (2009). Identification of a novel non-functional CYP2D6 allele, CYP2D6*69, in a Caucasian poor metabolizer individual. Eur J Clin Pharmacol 65:97–100.
  • Gaedigk, A., Gaedigk, R. Leeder, J. S. (2005b). CYP2D7 splice variants in human liver and brain: does CYP2D7 encode functional protein? Biochem Biophys Res Commun 336:1241–1250.
  • Gaedigk, A., Ndjountche, L., Divakaran, K., Dianne Bradford, L., Zineh, I., Oberlander, T. F., Brousseau, D. C., McCarver, D. G., Johnson, J. A., Alander, S. W., Wayne Riggs K., Steven Leeder, J. (2007b). Cytochrome P4502D6 (CYP2D6) gene locus heterogeneity: characterization of gene duplication events. Clin Pharmacol Ther 81:242–251.
  • Gaedigk, A., Ndjountche, L., Gaedigk, R., Leeder, J. S. Bradford, L. D. (2003a). Discovery of a novel nonfunctional cytochrome P450 2D6 allele, CYP2D642, in African American subjects. Clin Pharmacol Ther 73:575–576.
  • Gaedigk, A., Ndjountche, L., Leeder, J. S. Bradford, L. D. (2005c). Limited association of the 2988g > a single-nucleotide polymorphism with CYP2D641 in black subjects. Clin Pharmacol Ther 77:228–230; author reply, 230-221.
  • Gaedigk, A., Ryder, D. L., Bradford, L. D. Leeder, J. S. (2003b). CYP2D6 poor metabolizer status can be ruled out by a single genotyping assay for the −1584G promoter polymorphism. Clin Chem 49:1008–1011.
  • Gafni, I., Busto, U. E., Tyndale, R. F., Kaplan, H. L. Sellers, E. M. (2003). The role of cytochrome P450 2C19 activity in flunitrazepam metabolism in vivo. J Clin Psychopharmacol 23:169–175.
  • Gage, B. F., Eby, C., Milligan, P. E., Banet, G. A., Duncan, J. R. McLeod, H. L. (2004). Use of pharmacogenetics and clinical factors to predict the maintenance dose of warfarin. Thromb Haemost 91:87–94.
  • Gage, B. F. Lesko, L. J. (2008). Pharmacogenetics of warfarin: regulatory, scientific, and clinical issues. J Thromb Thrombolysis 25:45–51.
  • Gaikovitch, E. A., Cascorbi, I., Mrozikiewicz, P. M., Brockmoller, J., Frotschl, R., Kopke, K., Gerloff, T., Chernov, J. N. Roots, I. (2003). Polymorphisms of drug-metabolizing enzymes CYP2C9, CYP2C19, CYP2D6, CYP1A1, NAT2, and of P-glycoprotein in a Russian population. Eur J Clin Pharmacol 59:303–312.
  • Gamboa da Costa, G., Hamilton, L. P., Beland, F. A. Marques, M. M. (2000). Characterization of the major DNA adduct formed by alpha-hydroxy-N-desmethyltamoxifen in vitro and in vivo. Chem Res Toxicol 13:200–207.
  • Gan, S. H., Ismail, R., Wan Adnan, W. A. Zulmi, W. (2007). Impact of CYP2D6 genetic polymorphism on tramadol pharmacokinetics and pharmacodynamics. Mol Diagn Ther 11:171–181.
  • Garcia-Barcelo, M., Chow, L. Y., Lam, K. L., Chiu, H. F., Wing, Y. K. Waye, M. M. (2000). Occurrence of CYP2D6 gene duplication in Hong Kong Chinese. Clin Chem 46:1411–1413.
  • Garcia-Martin, E., Martinez, C., Pizarro, R. M., Garcia-Gamito, F. J., Gullsten, H., Raunio, H. Agundez, J. A. G. (2002). CYP3A4 variant alleles in white individuals with low CYP3A4 enzyme activity. Clin Pharmacol Ther 71:196–204.
  • Garcia-Martin, E., Martinez, C., Tabares, B., Frias, J. Agundez, J. A. (2004). Interindividual variability in ibuprofen pharmacokinetics is related to interaction of cytochrome P450 2C8 and 2C9 amino acid polymorphisms. Clin Pharmacol Ther 76:119–127.
  • Garcia-Quetglas, E., Azanza, J. R., Sadaba, B., Munoz, M. J., Gil, I. Campanero, M. A. (2007). Pharmacokinetics of tramadol enantiomers and their respective phase I metabolites in relation to CYP2D6 phenotype. Pharmacol Res 55:122–130.
  • Gardiner, S. J. Begg, E. J. (2006). Pharmacogenetics, drug-metabolizing enzymes, and clinical practice. Pharmacol Rev 58:521–590.
  • Garrido, M. J. Troconiz, I. F. (1999). Methadone: a review of its pharmacokinetic/pharmacodynamic properties. J Pharmacol Toxicol Methods 42:61–66.
  • Gasparini, L., Ongini, E. Wenk, G. (2004). Nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer’s disease: old and new mechanisms of action. J Neurochem 91:521–536.
  • Gatanaga, H., Hayashida, T., Tsuchiya, K., Yoshino, M., Kuwahara, T., Tsukada, H., Fujimoto, K., Sato, I., Ueda, M., Horiba, M., Hamaguchi, M., Yamamoto, M., Takata, N., Kimura, A., Koike, T., Gejyo, F., Matsushita, S., Shirasaka, T., Kimura, S. Oka, S. (2007). Successful efavirenz dose reduction in HIV type 1-infected individuals with cytochrome P450 2B6 *6 and *26. Clin Infect Dis 45:1230–1237.
  • Gawronska-Szklarz, B., Wrzesniewska, J., Starzynska, T., Pawlik, A., Safranow, K., Ferenc, K. Drozdzik, M. (2005). Effect of CYP2C19 and MDR1 polymorphisms on cure rate in patients with acid-related disorders with Helicobacter pylori infection. Eur J Clin Pharmacol 61:375–379.
  • Geerts, H. (2007). Drug evaluation: (R)-flurbiprofen—an enantiomer of flurbiprofen for the treatment of Alzheimer’s disease. Drugs 10:121–133.
  • Gellner, K., Eiselt, R., Hustert, E., Arnold, H., Koch, I., Haberl, M., Deglmann, C. J., Burk, O., Buntefuss, D., Escher, S., Bishop, C., Koebe, H. G., Brinkmann, U., Klenk, H. P., Kleine, K., Meyer, U. A. Wojnowski, L. (2001). Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene. Pharmacogenetics 11:111–121.
  • Gerber, J. G., Rhodes, R. J. Gal, J. (2004). Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19. Chirality 16:36–44.
  • Gervot, L., Rochat, B., Gautier, J. C., Bohnenstengel, F., Kroemer, H., de Berardinis, V., Martin, H., Beaune, P., de Waziers, I. (1999). Human CYP2B6: expression, inducibility, and catalytic activities. Pharmacogenetics 9:295–306.
  • Ghotbi, R., Christensen, M., Roh, H. K., Ingelman-Sundberg, M., Aklillu, E. Bertilsson, L. (2007). Comparisons of CYP1A2 genetic polymorphisms, enzyme activity, and the genotype-phenotype relationship in Swedes and Koreans. Eur J Clin Pharmacol 63:537–546.
  • Giancarlo, G. M., Venkatakrishnan, K., Granda, B. W., von Moltke, L. L. Greenblatt, D. J. (2001). Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: inhibition by sulfaphenazole, omeprazole, and ticlopidine. Eur J Clin Pharmacol 57:31–36.
  • Gibbs, J. P., Hyland, R. Youdim, K. (2006). Minimizing polymorphic metabolism in drug discovery: evaluation of the utility of in vitro methods for predicting pharmacokinetic consequences associated with CYP2D6 metabolism. Drug Metab Dispos 34:1516–1522.
  • Giessmann, T., Modess, C., Hecker, U., Zschiesche, M., Dazert, P., Kunert-Keil, C., Warzok, R., Engel, G., Weitschies, W., Cascorbi, I., Kroemer, H. K. Siegmund, W. (2004). CYP2D6 genotype and induction of intestinal drug transporters by rifampin predict presystemic clearance of carvedilol in healthy subjects. Clin Pharmacol Ther 75:213–222.
  • Gilham, D. E., Cairns, W., Paine, M. J., Modi, S., Poulsom, R., Roberts, G. C. Wolf, C. R. (1997). Metabolism of MPTP by cytochrome P4502D6 and the demonstration of 2D6 mRNA in human foetal and adult brain by in situ hybridization. Xenobiotica 27:111–125.
  • Gillam, E. M., Baba, T., Kim, B. R., Ohmori, S. Guengerich, F. P. (1993). Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch Biochem Biophys 305:123–131.
  • Giraud, C., Tran, A., Rey, E., Vincent, J., Treluyer, J. M. Pons, G. (2004). In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos 32:1279–1286.
  • Givens, R. C., Lin, Y. S., Dowling, A. L., Thummel, K. E., Lamba, J. K., Schuetz, E. G., Stewart, P. W. Watkins, P. B. (2003). CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults. J Appl Physiol 95:1297–1300.
  • Gjerde, J., Hauglid, M., Breilid, H., Lundgren, S., Varhaug, J. E., Kisanga, E. R., Mellgren, G., Steen, V. M. Lien, E. A. (2008). Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Ann Oncol 19:56–61.
  • Glatt, H., Davis, W., Meinl, W., Hermersdorfer, H., Venitt, S. Phillips, D. H. (1998). Rat, but not human, sulfotransferase activates a tamoxifen metabolite to produce DNA adducts and gene mutations in bacteria and mammalian cells in culture. Carcinogenesis 19:1709–1713.
  • Goda, R., Nagai, D., Akiyama, Y., Nishikawa, K., Ikemoto, I., Aizawa, Y., Nagata, K. Yamazoe, Y. (2006). Detection of a new N-oxidized metabolite of flutamide, N-[4-nitro-3-(trifluoromethyl)phenyl]hydroxylamine, in human liver microsomes and urine of prostate cancer patients. Drug Metab Dispos 34:828–835.
  • Goetz, M. P., Kamal, A. Ames, M. M. (2008). Tamoxifen pharmacogenomics: the role of CYP2D6 as a predictor of drug response. Clin Pharmacol Ther 83:160–166.
  • Goetz, M. P., Knox, S. K., Suman, V. J., Rae, J. M., Safgren, S. L., Ames, M. M., Visscher, D. W., Reynolds, C., Couch, F. J., Lingle, W. L., Weinshilboum, R. M., Fritcher, E. G., Nibbe, A. M., Desta, Z., Nguyen, A., Flockhart, D. A., Perez, E. A. Ingle, J. N. (2007). The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat 101:113–121.
  • Goetz, M. P., Rae, J. M., Suman, V. J., Safgren, S. L., Ames, M. M., Visscher, D. W., Reynolds, C., Couch, F. J., Lingle, W. L., Flockhart, D. A., Desta, Z., Perez, E. A. Ingle, J. N. (2005). Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flashes. J Clin Oncol 23:9312–9318.
  • Golab-Janowska, M., Honczarenko, K., Gawronska-Szklarz, B. Potemkowski, A. (2007). CYP2D6 gene polymorphism as a probable risk factor for Alzheimer’s disease and Parkinson’s disease with dementia. Neurol Neurochir Pol 41:113–121.
  • Goldberg, R. Roth, D. (1996). Evaluation of fluvastatin in the treatment of hypercholesterolemia in renal transplant recipients taking cyclosporine. Transplantation 62:1559–1564.
  • Golden, R. N., De Vane, C. L., Laizure, S. C., Rudorfer, M. V., Sherer, M. A. Potter, W. Z. (1988). Bupropion in depression. II. The role of metabolites in clinical outcome. Arch Gen Psychiatry 45:145–149.
  • Gonzalez, F. J., Matsunaga, T., Nagata, K., Meyer, U. A., Nebert, D. W., Pastewka, J., Kozak, C. A., Gillette, J., Gelboin, H. V. Hardwick, J. P. (1987). Debrisoquine 4-hydroxylase: characterization of a new P450 gene subfamily, regulation, chromosomal mapping, and molecular analysis of the DA rat polymorphism. DNA 6:149–161.
  • Gonzalez, F. J., Schmid, B. J., Umeno, M., McBride, O. W., Hardwick, J. P., Meyer, U. A., Gelboin, H. V. Idle, J. R. (1988a). Human P450PCN1: sequence, chromosome localization, and direct evidence through cDNA expression that P450PCN1 is nifedipine oxidase. DNA 7: 79–86.
  • Gonzalez, F. J., Skoda, R. C., Kimura, S., Umeno, M., Zanger, U. M., Nebert, D. W., Gelboin, H. V., Hardwick, J. P. Meyer, U. A. (1988b). Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature 331:442–446.
  • Goodman, M. T., McDuffie, K., Kolonel, L. N., Terada, K., Donlon, T. A., Wilkens, L. R., Guo, C. Le Marchand, L. (2001). Case-control study of ovarian cancer and polymorphisms in genes involved in catecholestrogen formation and metabolism. Cancer Epidemiol Biomarkers Prev 10:209–216.
  • Goodstadt, L. Ponting, C. P. (2004). Vitamin K epoxide reductase: homology, active site, and catalytic mechanism. Trends Biochem Sci 29:289–292.
  • Goodwin, B., Hodgson, E. Liddle, C. (1999). The orphan human pregnane X receptor mediates the transcriptional activation of CYP3A4 by rifampicin through a distal enhancer module. Mol Pharmacol 56:1329–1339.
  • Goodwin, B., Moore, L. B., Stoltz, C. M., McKee, D. D. Kliewer, S. A. (2001). Regulation of the human CYP2B6 gene by the nuclear pregnane X receptor. Mol Pharmacol 60:427–431.
  • Gorman, G. S., Coward, L., Kerstner-Wood, C., Cork, L., Kapetanovic, I. M., Brouillette, W. J. Muccio, D. D. (2007). In vitro metabolic characterization, phenotyping, and kinetic studies of 9cUAB30, a retinoid X receptor-specific retinoid. Drug Metab Dispos 35:1157–1164.
  • Gorski, J. C., Jones, D. R., Hamman, M. A., Wrighton, S. A. Hall, S. D. (1999). Biotransformation of alprazolam by members of the human cytochrome P4503A subfamily. Xenobiotica 29:931–944.
  • Gothard, P. Rogers, T. R. (2004). Voriconazole for serious fungal infections. Int J Clin Pract 58:74–80.
  • Goto, A., Adachi, Y., Inaba, A., Nakajima, H., Kobayashi, H. Sakai, K. (2004). Identification of human p450 isoforms involved in the metabolism of the antiallergic drug, oxatomide, and its inhibitory effect on enzyme activity. Biol Pharm Bull 27:684–690.
  • Gotoh, O. (1992). Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences. J Biol Chem 267:83–90.
  • Gough, A. C., Miles, J. S., Spurr, N. K., Moss, J. E., Gaedigk, A., Eichelbaum, M. Wolf, C. R. (1990). Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature 347:773–776.
  • Gram, L. F., Brosen, K., Kragh-Sorensen, P. Christensen, P. (1989). Steady-state plasma levels of E- and Z-10-OH-nortriptyline in nortriptyline-treated patients: significance of concurrent medication and the sparteine oxidation phenotype. Ther Drug Monit 11:508–514.
  • Gram, L. F. Christiansen, J. (1975). First-pass metabolism of imipramine in man. Clin Pharmacol Ther 17:555–563.
  • Gram, L. F., Guentert, T. W., Grange, S., Vistisen, K. Brosen, K. (1995). Moclobemide, a substrate of CYP2C19 and an inhibitor of CYP2C19, CYP2D6, and CYP1A2: a panel study. Clin Pharmacol Ther 57:670–677.
  • Granfors, M. T., Backman, J. T., Laitila, J. Neuvonen, P. J. (2004). Tizanidine is mainly metabolized by cytochrome p450 1A2 in vitro. Br J Clin Pharmacol 57:349–353.
  • Grant, A. O. (1996). Propafenone: an effective agent for the management of supraventricular arrhythmias. J Cardiovasc Electrophysiol 7:353–364.
  • Granvil, C. P., Madan, A., Sharkawi, M., Parkinson, A. Wainer, I. W. (1999). Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes. Drug Metab Dispos 27:533–541.
  • Gray, I. C., Nobile, C., Muresu, R., Ford, S. Spurr, N. K. (1995). A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24. Genomics 28:328–332.
  • Greene, M. F. (2000). Oral hypoglycemic drugs for gestational diabetes. N Engl J Med 343:1178–1179.
  • Griese, E. U., Asante-Poku, S., Ofori-Adjei, D., Mikus, G. Eichelbaum, M. (1999). Analysis of the CYP2D6 gene mutations and their consequences for enzyme function in a West African population. Pharmacogenetics 9:715–723.
  • Griese, E. U., Zanger, U. M., Brudermanns, U., Gaedigk, A., Mikus, G., Morike, K., Stuven, T. Eichelbaum, M. (1998). Assessment of the predictive power of genotypes for the in-vivo catalytic function of CYP2D6 in a German population. Pharmacogenetics 8:15–26.
  • Groeneveld, G. J., van Kan, H. J., Lie, A. H. L., Guchelaar, H. J. van den Berg, L. H. (2008). An association study of riluzole serum concentration and survival and disease progression in patients with ALS. Clin Pharmacol Ther 83:718–722.
  • Gromada, J., Dissing, S., Kofod, H. Frokjaer-Jensen, J. (1995). Effects of the hypoglycaemic drugs repaglinide and glibenclamide on ATP-sensitive potassium-channels and cytosolic calcium levels in beta TC3 cells and rat pancreatic beta cells. Diabetologia 38:1025–1032.
  • Groopman, J. D., Kensler, T. W. Wild, C. P. (2008). Protective interventions to prevent aflatoxin-induced carcinogenesis in developing countries. Annu Rev Public Health 29:187–203.
  • Gross, A. S., Mikus, G., Fischer, C. Eichelbaum, M. (1991). Polymorphic flecainide disposition under conditions of uncontrolled urine flow and pH. Eur J Clin Pharmacol 40:155–162.
  • Gross, A. S., Mikus, G., Fischer, C., Hertrampf, R., Gundert-Remy, U. Eichelbaum, M. (1989). Stereoselective disposition of flecainide in relation to the sparteine/debrisoquine metaboliser phenotype. Br J Clin Pharmacol 28:555–566.
  • Grygiel, J. J. Birkett, D. J. (1980). Effect of age on patterns of theophylline metabolism. Clin Pharmacol Ther 28:456–462.
  • Gu, J., Su, T., Chen, Y., Zhang, Q. Y. Ding, X. (2000). Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity. Toxicol Appl Pharmacol 165:158–162.
  • Gu, L., Gonzalez, F. J., Kalow, W. Tang, B. K. (1992). Biotransformation of caffeine, paraxanthine, theobromine, and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics 2:73–77.
  • Guengerich, F. P. Shimada, T. (1998). Activation of procarcinogens by human cytochrome P450 enzymes. Mutat Res 400:201–213.
  • Guidice, J. M., Marez, D., Sabbagh, N., Legrand-Andreoletti, M., Spire, C., Alcaide, E., Lafitte, J. J. Broly, F. (1997). Evidence for CYP2D6 expression in human lung. Biochem Biophys Res Commun 241:79–85.
  • Guitton, J., Buronfosse, T., Desage, M., Flinois, J. P., Perdrix, J. P., Brazier, J. L. Beaune, P. (1998). Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth 80:788–795.
  • Gundert-Remy, U., Hildebrandt, R., Hengen, N. Weber, E. (1983). Nonlinear elimination processes of theophylline. Eur J Clin Pharmacol 24:71–78.
  • Gunes, A. Dahl, M. L. (2008). Variation in CYP1A2 activity and its clinical implications: influence of environmental factors and genetic polymorphisms. Pharmacogenomics 9:625–637.
  • Guo, Y., Wang, Y., Si, D., Fawcett, P. J., Zhong, D. Zhou, H. (2005a). Catalytic activities of human cytochrome P450 2C9*1, 2C9*3, and 2C9*13. Xenobiotica 35:, 853–861.
  • Guo, Y., Zhang, Y., Wang, Y., Chen, X., Si, D., Zhong, D., Fawcett, J. P. Zhou, H. (2005b). Role of CYP2C9 and its variants (CYP2C9*3 and CYP2C9*13) in the metabolism of lornoxicam in humans. Drug Metab Dispos 33:749–753.
  • Guo, Z., Gillam, E. M., Ohmori, S., Tukey, R. H. Guengerich, F. P. (1994). Expression of modified human cytochrome P450 1A1 in Escherichia coli: effects of 5’ substitution, stabilization, purification, spectral characterization, and catalytic properties. Arch Biochem Biophys 312:436–446.
  • Gut, J., Catin, T., Dayer, P., Kronbach, T., Zanger, U. Meyer, U. A. (1986). Debrisoquine/sparteine-type polymorphism of drug oxidation. Purification and characterization of two functionally different human liver cytochrome P-450 isozymes involved in impaired hydroxylation of the prototype substrate bufuralol. J Biol Chem 261:11734–11743.
  • Gut, J., Gasser, R., Dayer, P., Kronbach, T., Catin, T. Meyer, U. A. (1984). Debrisoquine-type polymorphism of drug oxidation: purification from human liver of a cytochrome P450 isozyme with high activity for bufuralol hydroxylation. FEBS Lett 173:287–290.
  • Guzey, C., Aamo, T. Spigset, O. (2000). Risperidone metabolism and the impact of being a cytochrome P450 2D6 ultrarapid metabolizer. J Clin Psychiatry 61:600–601.
  • Ha-Duong, N. T., Dijols, S., Macherey, A. C., Goldstein, J. A., Dansette, P. M. Mansuy, D. (2001). Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19. Biochemistry 40:12112–12122.
  • Ha, H. R., Chen, J., Freiburghaus, A. U. Follath, F. (1995). Metabolism of theophylline by cDNA-expressed human cytochromes P-450. Br J Clin Pharmacol 39:321–326.
  • Haas, D. W., Bartlett, J. A., Andersen, J. W., Sanne, I., Wilkinson, G. R., Hinkle, J., Rousseau, F., Ingram, C. D., Shaw, A., Lederman, M. M. Kim, R. B. (2006). Pharmacogenetics of nevirapine-associated hepatotoxicity: an Adult AIDS Clinical Trials Group collaboration. Clin Infect Dis 43:783–786.
  • Haas, D. W., Ribaudo, H. J., Kim, R. B., Tierney, C., Wilkinson, G. R., Gulick, R. M., Clifford, D. B., Hulgan, T., Marzolini, C. Acosta, E. P. (2004). Pharmacogenetics of efavirenz and central nervous system side effects: an Adult AIDS Clinical Trials Group study. Aids 18:2391–2400.
  • Haas, D. W., Smeaton, L. M., Shafer, R. W., Robbins, G. K., Morse, G. D., Labbe, L., Wilkinson, G. R., Clifford, D. B., D’Aquila, R. T., De Gruttola, V., Pollard, R. B., Merigan, T. C., Hirsch, M. S., George, A. L., Jr., Donahue, J. P. Kim, R. B. (2005). Pharmacogenetics of long-term responses to antiretroviral regimens containing efavirenz and/or nelfinavir: an Adult Aids Clinical Trials Group study. J Infect Dis 192:1931–1942.
  • Haberl, M., Anwald, B., Klein, K., Weil, R., Fuss, C., Gepdiremen, A., Zanger, U. M., Meyer, U. A. Wojnowski, L. (2005). Three haplotypes associated with CYP2A6 phenotypes in Caucasians. Pharmacogenet Genomics 15:609–624.
  • Hadama, A., Ieiri, I., Morita, T., Kimura, M., Urae, A., Irie, S., Kaneda, T., Mamiya, K., Tashiro, N., Higuchi, S. Otsubo, K. (2001). P-hydroxylation of phenobarbital: relationship to (S)-mephenytoin hydroxylation (CYP2C19) polymorphism. Ther Drug Monit 23:115–118.
  • Hadidi, H., Irshaid, Y., Vagbo, C. B., Brunsvik, A., Cholerton, S., Zahlsen, K. Idle, J. R. (1998). Variability of coumarin 7- and 3-hydroxylation in a Jordanian population is suggestive of a functional polymorphism in cytochrome P450 CYP2A6. Eur J Clin Pharmacol 54:437–441.
  • Hadidi, H., Zahlsen, K., Idle, J. R. Cholerton, S. (1997). A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin. Food Chem Toxicol 35:903–907.
  • Haefeli, W. E., Bargetzi, M. J., Follath, F. Meyer, U. A. (1990). Potent inhibition of cytochrome P450IID6 (debrisoquin 4-hydroxylase) by flecainide in vitro and in vivo. J Cardiovasc Pharmacol 15:776–779.
  • Haefeli, W. E., Vozeh, S., Ha, H. R., Taeschner, W. Follath, F. (1991). Concentration-effect relations of 5-hydroxypropafenone in normal subjects. Am J Cardiol 67:1022–1026.
  • Haining, R. L., Hunter, A. P., Veronese, M. E., Trager, W. F. Rettie, A. E. (1996). Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Arch Biochem Biophys 333:447–458.
  • Hakkola, J., Pasanen, M., Hukkanen, J., Pelkonen, O., Maenpaa, J., Edwards, R. J., Boobis, A. R. Raunio, H. (1996a). Expression of xenobiotic-metabolizing cytochrome P450 forms in human full-term placenta. Biochem Pharmacol 51:403–411.
  • Hakkola, J., Pasanen, M., Purkunen, R., Saarikoski, S., Pelkonen, O., Maenpaa, J., Rane, A. Raunio, H. (1994). Expression of xenobiotic-metabolizing cytochrome P450 forms in human adult and fetal liver. Biochem Pharmacol 48:59–64.
  • Hakkola, J., Raunio, H., Purkunen, R., Pelkonen, O., Saarikoski, S., Cresteil, T. Pasanen, M. (1996b). Detection of cytochrome P450 gene expression in human placenta in first trimester of pregnancy. Biochem Pharmacol 52:379–383.
  • Hall, S. D., Hamman, M. A., Rettie, A. E., Wienkers, L. C., Trager, W. F., Vandenbranden, M. Wrighton, S. A. (1994). Relationships between the levels of cytochrome P4502C9 and its prototypic catalytic activities in human liver microsomes. Drug Metab Dispos 22:975–978.
  • Hallberg, P., Karlsson, J., Kurland, L., Lind, L., Kahan, T., Malmqvist, K., Ohman, K. P., Nystrom, F. Melhus, H. (2002). The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) trial. J Hypertens 20:2089–2093.
  • Halling, J., Weihe, P. Brosen, K. (2008a). The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population. Br J Clin Pharmacol 65:134–138.
  • Halling, J., Weihe, P. Brosen, K. (2008b). CYP2D6 polymorphism in relation to tramadol metabolism: a study of faroese patients. Ther Drug Monit 30:271–275.
  • Hamelin, B. A., Bouayad, A., Methot, J., Jobin, J., Desgagnes, P., Poirier, P., Allaire, J., Dumesnil, J. Turgeon, J. (2000). Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clin Pharmacol Ther 67:466–477.
  • Hamelin, B. A., Turgeon, J., Vallee, F., Belanger, P. M., Paquet, F. LeBel, M. (1996). The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. Clin Pharmacol Ther 60:512–521.
  • Hamman, M. A., Thompson, G. A. Hall, S. D. (1997). Regioselective and stereoselective metabolism of ibuprofen by human cytochrome P450 2C. Biochem Pharmacol 54:33–41.
  • Hammer, S. M., Eron, J. J., Jr., Reiss, P., Schooley, R. T., Thompson, M. A., Walmsley, S., Cahn, P., Fischl, M. A., Gatell, J. M., Hirsch, M. S., Jacobsen, D. M., Montaner, J. S., Richman, D. D., Yeni, P. G. Volberding, P. A. (2008). Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 300:555–570.
  • Hamzeiy, H., Vahdati-Mashhadian, N., Edwards, H. J. Goldfarb, P. S. (2002). Mutation analysis of the human CYP3A4 gene 5’ regulatory region: population screening using non-radioactive SSCP. Mutat Res 500:103–110.
  • Han, X. M., Ouyang, D. S., Chen, X. P., Shu, Y., Jiang, C. H., Tan, Z. R. Zhou, H. H. (2002). Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2. Br J Clin Pharmacol 54:540–543.
  • Hanioka, N., Kimura, S., Meyer, U. A. Gonzalez, F. J. (1990). The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934—a base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3’ splice recognition site. Am J Hum Genet 47:994–1001.
  • Hanioka, N., Tsuneto, Y., Saito, Y., Sumada, T., Maekawa, K., Saito, K., Sawada, J. Narimatsu, S. (2007). Functional characterization of two novel CYP2C19 variants (CYP2C19*18 and CYP2C19*19) found in a Japanese population. Xenobiotica 37:342–355.
  • Hanna, I. H., Krauser, J. A., Cai, H., Kim, M. S. Guengerich, F. P. (2001). Diversity in mechanisms of substrate oxidation by cytochrome P450 2D6. Lack of an allosteric role of NADPH-cytochrome P450 reductase in catalytic regioselectivity. J Biol Chem 276:39553–39561.
  • Hanna, I. H., Reed, J. R., Guengerich, F. P. Hollenberg, P. F. (2000). Expression of human cytochrome P450 2B6 in Escherichia coli: characterization of catalytic activity and expression levels in human liver. Arch Biochem Biophys 376:206–216.
  • Hara, Y., Nakajima, M., Miyamoto, K. I. Yokoi, T. (2005). Inhibitory effects of psychotropic drugs on mexiletine metabolism in human liver microsomes: prediction of in vivo drug interactions. Xenobiotica 35:549–560.
  • Haria, M., Fitton, A. McTavish, D. (1994). Trazodone. A review of its pharmacology, therapeutic use in depression, and therapeutic potential in other disorders. Drugs Aging 4:331–355.
  • Hariparsad, N., Nallani, S. C., Sane, R. S., Buckley, D. J., Buckley, A. R. Desai, P. B. (2004). Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J Clin Pharmacol 44:1273–1281.
  • Haritos, V. S., Ghabrial, H., Ahokas, J. T. Ching, M. S. (2000). Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin. Pharmacogenetics 10:591–603.
  • Hartter, S., Korhonen, T., Lundgren, S., Rane, A., Tolonen, A., Turpeinen, M. Laine, K. (2006). Effect of caffeine intake 12 or 24 hours prior to melatonin intake and CYP1A2*1F polymorphism on CYP1A2 phenotyping by melatonin. Basic Clin Pharmacol Toxicol 99:300–304.
  • Hartter, S., Nordmark, A., Rose, D. M., Bertilsson, L., Tybring, G. Laine, K. (2003). Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br J Clin Pharmacol 56:679–682.
  • Hartter, S., Tybring, G., Friedberg, T., Weigmann, H. Hiemke, C. (2002). The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19. Pharm Res 19:1034–1037.
  • Hartter, S., Ursing, C., Morita, S., Tybring, G., von Bahr, C., Christensen, M., Rojdmark, S., Bertilsson, L. (2001a). Orally given melatonin may serve as a probe drug for cytochrome P450 1A2 activity in vivo: a pilot study. Clin Pharmacol Ther 70:10–16.
  • Hartter, S., Wang, X., Weigmann, H., Friedberg, T., Arand, M., Oesch, F. Hiemke, C. (2001b). Differential effects of fluvoxamine and other antidepressants on the biotransformation of melatonin. J Clin Psychopharmacol 21:167–174.
  • Hasemann, C. A., Kurumbail, R. G., Boddupalli, S. S., Peterson, J. A. Deisenhofer, J. (1995). Structure and function of cytochromes P450: a comparative analysis of three crystal structures. Structure 3:41–62.
  • Hashimoto, H., Toide, K., Kitamura, R., Fujita, M., Tagawa, S., Itoh, S. Kamataki, T. (1993). Gene structure of CYP3A4, an adult specific form of cytochrome P450 in human livers, and its transcriptional control. Eur J Biochem 218:585–595.
  • Hatorp, V., Hansen, K. T. Thomsen, M. S. (2003). Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide. J Clin Pharmacol 43:649–660.
  • Haufroid, V., Mourad, M., Van Kerckhove, V., Wawrzyniak, J., De Meyer, M., Eddour, D. C., Malaise, J., Lison, D., Squifflet, J. P. Wallemacq, P. (2004). The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 14:147–154.
  • Havlir, D., Cheeseman, S. H., McLaughlin, M., Murphy, R., Erice, A., Spector, S. A., Greenough, T. C., Sullivan, J. L., Hall, D., Myers, M. et al. (1995). High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection. J Infect Dis 171:537–545.
  • Hayashi, S., Watanabe, J., Nakachi, K. Kawajiri, K. (1991). Genetic linkage of lung cancer-associated MspI polymorphism with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene. J Biochem 110:407–411.
  • He, X. Y., Shen, J., Ding, X., Lu, A. Y. Hong, J. Y. (2004a). Identification of critical amino acid residues of human CYP2A13 for the metabolic activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, a tobacco-specific carcinogen. Drug Metab Dispos 32:1516–1521.
  • He, X. Y., Shen, J., Hu, W. Y., Ding, X., Lu, A. Y. Hong, J. Y. (2004b). Identification of Val117 and Arg372 as critical amino acid residues for the activity difference between human CYP2A6 and CYP2A13 in coumarin 7-hydroxylation. Arch Biochem Biophys 427:143–153.
  • He, X. Y., Tang, L., Wang, S. L., Cai, Q. S., Wang, J. S. Hong, J. Y. (2006). Efficient activation of aflatoxin B1 by cytochrome P450 2A13, an enzyme predominantly expressed in human respiratory tract. Int J Cancer 118:2665–2671.
  • Hecht, S. S., Hochalter, J. B., Villalta, P. W. Murphy, S. E. (2000). 2’-hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: formation of a lung carcinogen precursor. Proc Natl Acad Sci U S A 97:12493–12497.
  • Hefler, L. A., Tempfer, C. B., Grimm, C., Lebrecht, A., Ulbrich, E., Heinze, G., Leodolter, S., Schneeberger, C., Mueller, M. W., Muendlein, A. Koelbl, H. (2004). Estrogen-metabolizing gene polymorphisms in the assessment of breast carcinoma risk and fibroadenoma risk in Caucasian women. Cancer 101:264–269.
  • Hege, H. G., Hollmann, M., Kaumeier, S. Lietz, H. (1984). The metabolic fate of 2H-labelled propafenone in man. Eur J Drug Metab Pharmacokinet 9:41–55.
  • Heim, M. Meyer, U. A. (1990). Genotyping of poor metabolisers of debrisoquine by allele-specific PCR amplification. Lancet 336:529–532.
  • Heim, M. H. Meyer, U. A. (1992). Evolution of a highly polymorphic human cytochrome P450 gene cluster: CYP2D6. Genomics 14:49–58.
  • Helsby, N. A., Ward, S. A., Howells, R. E. Breckenridge, A. M. (1990). In vitro metabolism of the biguanide antimalarials in human liver microsomes: evidence for a role of the mephenytoin hydroxylase (P450 MP) enzyme. Br J Clin Pharmacol 30:287–291.
  • Helsby, N. A., Ward, S. A., Parslew, R. A., Friedmann, P. S. Rhodes, L. E. (1998). Hepatic cytochrome P450 CYP2C activity in psoriasis: studies using proguanil as a probe compound. Acta Derm Venereol 78:81–83.
  • Hemeryck, A., De Vriendt, C. A. Belpaire, F. M. (2001). Metoprolol-paroxetine interaction in human liver microsomes: stereoselective aspects and prediction of the in vivo interaction. Drug Metab Dispos 29:656–663.
  • Hemeryck, A., Lefebvre, R. A., De Vriendt, C., Belpaire, F. M. (2000). Paroxetine affects metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Clin Pharmacol Ther 67:283–291.
  • Henderson, B. E. Feigelson, H. S. (2000). Hormonal carcinogenesis. Carcinogenesis 21:427–433.
  • Hendset, M., Hermann, M., Lunde, H., Refsum, H. Molden, E. (2007). Impact of the CYP2D6 genotype on steady-state serum concentrations of aripiprazole and dehydroaripiprazole. Eur J Clin Pharmacol 63:1147–1151.
  • Henningsson, A., Marsh, S., Loos, W. J., Karlsson, M. O., Garsa, A., Mross, K., Mielke, S., Vigano, L., Locatelli, A., Verweij, J., Sparreboom, A. McLeod, H. L. (2005). Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel. Clin Cancer Res 11:8097–8104.
  • Herman, D., Peternel, P., Stegnar, M., Breskvar, K. Dolzan, V. (2006). A novel sequence variant in exon 7 of CYP2C9 gene (CYP2C9*24) in a patient on warfarin therapy. Thromb Haemost 95:192–194.
  • Hermann, M., Hendset, M., Fosaas, K., Hjerpset, M. Refsum, H. (2008). Serum concentrations of venlafaxine and its metabolites O-desmethylvenlafaxine and N-desmethylvenlafaxine in heterozygous carriers of the CYP2D6*3, *4, or *5 allele. Eur J Clin Pharmacol 64:483–487.
  • Hermans, J. J. Thijssen, H. H. (1993). Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity determines the differences in their pharmacokinetics. Br J Pharmacol 110:482–490.
  • Herraiz, T., Guillen, H., Aran, V. J., Idle, J. R. Gonzalez, F. J. (2006). Comparative aromatic hydroxylation and N-demethylation of MPTP neurotoxin and its analogs, N-methylated beta-carboline and isoquinoline alkaloids, by human cytochrome P450 2D6. Toxicol Appl Pharmacol 216:387–398.
  • Herrlin, K., Massele, A. Y., Rimoy, G., Alm, C., Rais, M., Ericsson, O., Bertilsson, L. Gustafsson, L. L. (2000). Slow chloroguanide metabolism in Tanzanians compared with white subjects and Asian subjects confirms a decreased CYP2C19 activity in relation to genotype. Clin Pharmacol Ther 68:189–198.
  • Herrlin, K., Yasui-Furukori, N., Tybring, G., Widen, J., Gustafsson, L. L. Bertilsson, L. (2003). Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes. Br J Clin Pharmacol 56:415–421.
  • Hesketh, P. J. (2008). Chemotherapy-induced nausea and vomiting. N Engl J Med 358:2482–2494.
  • Hesse, L. M., He, P., Krishnaswamy, S., Hao, Q., Hogan, K., von Moltke, L. L., Greenblatt, D. J. Court, M. H. (2004). Pharmacogenetic determinants of interindividual variability in bupropion hydroxylation by cytochrome P450 2B6 in human liver microsomes. Pharmacogenetics 14:225–238.
  • Hesse, L. M., Venkatakrishnan, K., Court, M. H., von Moltke, L. L., Duan, S. X., Shader, R. I. Greenblatt, D. J. (2000). CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants. Drug Metab Dispos 28:1176–1183.
  • Hesse, L. M., Venkatakrishnan, K., von Moltke, L. L., Shader, R. I. Greenblatt, D. J. (2001). CYP3A4 is the major CYP isoform mediating the in vitro hydroxylation and demethylation of flunitrazepam. Drug Metab Dispos 29:133–140.
  • Hewitt, D. J. (2000). The use of NMDA-receptor antagonists in the treatment of chronic pain. Clin J Pain 16:S73–S79.
  • Heyn, H., White, R. B. Stevens, J. C. (1996). Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin. Drug Metab Dispos 24:948–954.
  • Hichiya, H., Tanaka-Kagawa, T., Soyama, A., Jinno, H., Koyano, S., Katori, N., Matsushima, E., Uchiyama, S., Tokunaga, H., Kimura, H., Minami, N., Katoh, M., Sugai, K., Goto, Y., Tamura, T., Yamamoto, N., Ohe, Y., Kunitoh, H., Nokihara, H., Yoshida, T., Minami, H., Saijo, N., Ando, M., Ozawa, S., Saito, Y. Sawada, J. (2005). Functional characterization of five novel CYP2C8 variants, G171S, R186X, R186G, K247R, and K383N, found in a Japanese population. Drug Metab Dispos 33:630–636.
  • Hidestrand, M., Oscarson, M., Salonen, J. S., Nyman, L., Pelkonen, O., Turpeinen, M. Ingelman-Sundberg, M. (2001). CYP2B6 and CYP2C19 as the major enzymes responsible for the metabolism of selegiline, a drug used in the treatment of Parkinson’s disease, as revealed from experiments with recombinant enzymes. Drug Metab Dispos 29:1480–1484.
  • Higashi, M. K., Veenstra, D. L., Kondo, L. M., Wittkowsky, A. K., Srinouanprachanh, S. L., Farin, F. M. Rettie, A. E. (2002). Association between CYP2C9 genetic variants and anticoagulation-related outcomes during warfarin therapy. JAMA 287:1690–1698.
  • Higgins, M. J., Rae, J. M., Flockhart, D. A., Hayes, D. F. Stearns, V. (2009). Pharmacogenetics of Tamoxifen: who should undergo CYP2D6 genetic testing? J Natl Compr Canc Netw 7:203–213.
  • Hijazi, Y. Boulieu, R. (2002). Contribution of CYP3A4, CYP2B6, and CYP2C9 isoforms to N-demethylation of ketamine in human liver microsomes. Drug Metab Dispos 30:853–858.
  • Hildebrand, C. E., Gonzalez, F. J., McBride, O. W. Nebert, D. W. (1985). Assignment of the human 2,4,7,8-tetrachlorodibenzo-p-dioxin-inducible cytochrome P1-450 gene to chromosome 15. Nucleic Acids Res 13:2009–2016.
  • Hilli, J., Korhonen, T., Turpeinen, M., Hokkanen, J., Mattila, S. Laine, K. (2008). The effect of oral contraceptives on the pharmacokinetics of melatonin in healthy subjects with CYP1A2 g.-163C>A polymorphism. J Clin Pharmacol 48:986–994.
  • Hirani, V. N., Raucy, J. L. Lasker, J. M. (2004). Conversion of the HIV protease inhibitor nelfinavir to a bioactive metabolite by human liver CYP2C19. Drug Metab Dispos 32:1462–1467.
  • Hiratsuka, M., Hinai, Y., Konno, Y., Nozawa, H., Konno, S. Mizugaki, M. (2004). Three novel single-nucleotide polymorphisms (SNPs) of the CYP2B6 gene in Japanese individuals. Drug Metab Pharmacokinet 19:155–158.
  • Hiroi, T., Chow, T., Imaoka, S. Funae, Y. (2002). Catalytic specificity of CYP2D isoforms in rat and human. Drug Metab Dispos 30:970–976.
  • Hiroi, T., Imaoka, S. Funae, Y. (1998). Dopamine formation from tyramine by CYP2D6. Biochem Biophys Res Commun 249:838–843.
  • Hirvonen, A., Husgafvel-Pursiainen, K., Anttila, S., Karjalainen, A. Vainio, H. (1993). Polymorphism in CYP1A1 and CYP2D6 genes: possible association with susceptibility to lung cancer. Environ Health Perspect 101(Suppl 3):109–112.
  • Hirvonen, A., Husgafvel-Pursiainen, K., Karjalainen, A., Anttila, S. Vainio, H. (1992). Point-mutational MspI and Ile-Val polymorphisms closely linked in the CYP1A1 gene: lack of association with susceptibility to lung cancer in a Finnish study population. Cancer Epidemiol Biomarkers Prev 1:485–489.
  • Ho, M. K., Mwenifumbo, J. C., Zhao, B., Gillam, E. M. Tyndale, R. F. (2008). A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent. Pharmacogenet Genomics 18:67–75.
  • Hoffman, S. M., Fernandez-Salguero, P., Gonzalez, F. J. Mohrenweiser, H. W. (1995). Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19. J Mol Evol 41:894–900.
  • Hoffman, S. M., Nelson, D. R. Keeney, D. S. (2001). Organization, structure, and evolution of the CYP2 gene cluster on human chromosome 19. Pharmacogenetics 11:687–698.
  • Hoffmann, K. J., Regardh, C. G., Aurell, M., Ervik, M. Jordo, L. (1980). The effect of impaired renal function on the plasma concentration and urinary excretion of metoprolol metabolites. Clin Pharmacokinet 5:181–191.
  • Hofmann, M. H., Blievernicht, J. K., Klein, K., Saussele, T., Schaeffeler, E., Schwab, M. Zanger, U. M. (2008). Aberrant splicing caused by single-nucleotide polymorphism c.516G>T [Q172H], a marker of CYP2B6*6, is responsible for decreased expression and activity of CYP2B6 in liver. J Pharmacol Exp Ther 325:284–292.
  • Hohorst, H. J., Draeger, U., Peter, G. Voelcker, G. (1976). The problem of oncostatic specificity of cyclophosphamide (NSC-26271): studies on reactions that control the alkylating and cytotoxic activity. Cancer Treat Rep 60:309–315.
  • Hojo, M., Nagasaka, Y., Katayama, O. Serizawa, I. (1981). [Pharmacological study of Mequitazine (LM-209). (V). Pharmacological actions of a main metabolite of LM-209, mequitazine sulfoxide (LM-209 SO) (author’s transl)]. Nippon Yakurigaku Zasshi 78:431–438.
  • Hokari, K., Sugiyama, T., Kato, M., Saito, M., Miyagishima, T., Kudo, M., Nishikawa, K., Ishizuka, J., Komatsu, Y., Mizushima, T., Kagaya, H., Hige, S., Takeda, H. Asaka, M. (2001). Efficacy of triple therapy with rabeprazole for Helicobacter pylori infection and CYP2C19 genetic polymorphism. Aliment Pharmacol Ther 15:1479–1484.
  • Holliday, S. M. Benfield, P. (1995). Venlafaxine. A review of its pharmacology and therapeutic potential in depression. Drugs 49:280–294.
  • Holm, K. J. Spencer, C. M. (2000). Bupropion: a review of its use in the management of smoking cessation. Drugs 59:1007–1024.
  • Holmes, B. Heel, R. C. (1985). Flecainide. A preliminary review of its pharmacodynamic properties and therapeutic efficacy. Drugs 29:1–33.
  • Holstein, A., Plaschke, A., Ptak, M., Egberts, E. H., El-Din, J., Brockmoller, J. Kirchheiner, J. (2005). Association between CYP2C9 slow metabolizer genotypes and severe hypoglycaemia on medication with sulphonylurea hypoglycaemic agents. Br J Clin Pharmacol 60:103–106.
  • Holt, S. K., Rossing, M. A., Malone, K. E., Schwartz, S. M., Weiss, N. S. Chen, C. (2007). Ovarian cancer risk and polymorphisms involved in estrogen catabolism. Cancer Epidemiol Biomarkers Prev 16:481–489.
  • Honda, M., Nozawa, T., Igarashi, N., Inoue, H., Arakawa, R., Ogura, Y., Okabe, H., Taguchi, M. Hashimoto, Y. (2005). Effect of CYP2D6*10 on the pharmacokinetics of R- and S-carvedilol in healthy Japanese volunteers. Biol Pharm Bull 28:1476–1479.
  • Hong, X., Zhang, S., Mao, G., Jiang, S., Zhang, Y., Yu, Y., Tang, G., Xing, H. Xu, X. (2005). CYP2C9*3 allelic variant is associated with metabolism of irbesartan in Chinese population. Eur J Clin Pharmacol 61:627–634.
  • Horai, Y., Kimura, M., Furuie, H., Matsuguma, K., Irie, S., Koga, Y., Nagahama, T., Murakami, M., Matsui, T., Yao, T., Urae, A. Ishizaki, T. (2001). Pharmacodynamic effects and kinetic disposition of rabeprazole in relation to CYP2C19 genotypes. Aliment Pharmacol Ther 15:793–803.
  • Horikiri, Y., Suzuki, T. Mizobe, M. (1998). Pharmacokinetics and metabolism of bisoprolol enantiomers in humans. J Pharm Sci 87:289–294.
  • Hoskins, J. M., Shenfield, G. M. Gross, A. S. (1998). Relationship between proguanil metabolic ratio and CYP2C19 genotype in a Caucasian population. Br J Clin Pharmacol 46:499–504.
  • Hsieh, K. P., Lin, Y. Y., Cheng, C. L., Lai, M. L., Lin, M. S., Siest, J. P. Huang, J. D. (2001). Novel mutations of CYP3A4 in Chinese. Drug Metab Dispos 29:268–273.
  • Hsyu, P. H., Singh, A., Giargiari, T. D., Dunn, J. A., Ascher, J. A. Johnston, J. A. (1997). Pharmacokinetics of bupropion and its metabolites in cigarette smokers versus nonsmokers. J Clin Pharmacol 37:737–743.
  • Hu, X., Srivastava, S. K., Xia, H., Awasthi, Y. C. Singh, S. V. (1996). An alpha class mouse glutathione S-transferase with exceptional catalytic efficiency in the conjugation of glutathione with 7beta, 8alpha-dihydroxy-9alpha,10alpha-oxy-7, 8,9,10-tetrahydrobenzo(a)pyrene. J Biol Chem 271: 32684–32688.
  • Huang, C. S., Chern, H. D., Chang, K. J., Cheng, C. W., Hsu, S. M. Shen, C. Y. (1999a). Breast cancer risk associated with genotype polymorphism of the estrogen-metabolizing genes CYP17, CYP1A1, and COMT: a multigenic study on cancer susceptibility. Cancer Res 59:4870–4875.
  • Huang, J. D., Guo, W. C., Lai, M. D., Guo, Y. L. Lambert, G. H. (1999b). Detection of a novel cytochrome P-450 1A2 polymorphism (F21L) in Chinese. Drug Metab Dispos 27:98–101.
  • Huang, Z., Fasco, M. J. Kaminsky, L. S. (1997). Alternative splicing of CYP2D mRNA in human breast tissue. Arch Biochem Biophys 343:101–108.
  • Hummel, M. A., Dickmann, L. J., Rettie, A. E., Haining, R. L. Tracy, T. S. (2004). Differential activation of CYP2C9 variants by dapsone. Biochem Pharmacol 67:1831–1841.
  • Hummel, M. A., Locuson, C. W., Gannett, P. M., Rock, D. A., Mosher, C. M., Rettie, A. E. Tracy, T. S. (2005). CYP2C9 genotype-dependent effects on in vitro drug-drug interactions: switching of benzbromarone effect from inhibition to activation in the CYP2C9.3 variant. Mol Pharmacol 68:644–651.
  • Hunfeld, N. G., Mathot, R. A., Touw, D. J., van Schaik, R. H., Mulder, P. G., Franck, P. F., Kuipers, E. J. Geus, W. P. (2008). Effect of CYP2C19*2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians. Br J Clin Pharmacol 65:752–760.
  • Hung, C. C., Lin, C. J., Chen, C. C., Chang, C. J. Liou, H. H. (2004). Dosage recommendation of phenytoin for patients with epilepsy with different CYP2C9/CYP2C19 polymorphisms. Ther Drug Monit 26:534–540.
  • Hurt, R. D., Sachs, D. P., Glover, E. D., Offord, K. P., Johnston, J. A., Dale, L. C., Khayrallah, M. A., Schroeder, D. R., Glover, P. N., Sullivan, C. R., Croghan, I. T. Sullivan, P. M. (1997). A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med 337:1195–1202.
  • Hustert, E., Haberl, M., Burk, O., Wolbold, R., He, Y. Q., Klein, K., Nuessler, A. C., Neuhaus, P., Klattig, J., Eiselt, R., Koch, I., Zibat, A., Brockmoller, J., Halpert, J. R., Zanger, U. M. Wojnowski, L. (2001). The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 11:773–779.
  • Hyland, R., Jones, B. C. Smith, D. A. (2003). Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab Dispos 31:540–547.
  • Hyttel, J., Bogeso, K. P., Perregaard, J. Sanchez, C. (1992). The pharmacological effect of citalopram residues in the (S)-(+)-enantiomer. J Neural Transm Gen Sect 88:157–160.
  • Ibeanu, G. C., Blaisdell, J., Ferguson, R. J., Ghanayem, B. I., Brosen, K., Benhamou, S., Bouchardy, C., Wilkinson, G. R., Dayer, P. Goldstein, J. A. (1999). A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin. J Pharmacol Exp Ther 290:635–640.
  • Ibeanu, G. C., Blaisdell, J., Ghanayem, B. I., Beyeler, C., Benhamou, S., Bouchardy, C., Wilkinson, G. R., Dayer, P., Daly, A. K. Goldstein, J. A. (1998a). An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. Pharmacogenetics 8:129–135.
  • Ibeanu, G. C., Goldstein, J. A., Meyer, U., Benhamou, S., Bouchardy, C., Dayer, P., Ghanayem, B. I. Blaisdell, J. (1998b). Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. J Pharmacol Exp Ther 286:1490–1495.
  • Ieiri, I., Kishimoto, Y., Okochi, H., Momiyama, K., Morita, T., Kitano, M., Morisawa, T., Fukushima, Y., Nakagawa, K., Hasegawa, J., Otsubo, K. Ishizaki, T. (2001). Comparison of the kinetic disposition of and serum gastrin change by lansoprazole versus rabeprazole during an 8-day dosing scheme in relation to CYP2C19 polymorphism. Eur J Clin Pharmacol 57:485–492.
  • Ieiri, I., Tainaka, H., Morita, T., Hadama, A., Mamiya, K., Hayashibara, M., Ninomiya, H., Ohmori, S., Kitada, M., Tashiro, N., Higuchi, S. Otsubo, K. (2000). Catalytic activity of three variants (Ile, Leu, and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. Ther Drug Monit 22:237–244.
  • Iida, I., Miyata, A., Arai, M., Hirota, M., Akimoto, M., Higuchi, S., Kobayashi, K. Chiba, K. (2004). Catalytic roles of CYP2C9 and its variants (CYP2C9*2 and CYP2C9*3) in lornoxicam 5’-hydroxylation. Drug Metab Dispos 32:7–9.
  • Ikeda, K., Yoshisue, K., Matsushima, E., Nagayama, S., Kobayashi, K., Tyson, C. A., Chiba, K. Kawaguchi, Y. (2000). Bioactivation of tegafur to 5-fluorouracil is catalyzed by cytochrome P-450 2A6 in human liver microsomes in vitro. Clin Cancer Res 6:4409–4415.
  • Ikeya, K., Jaiswal, A. K., Owens, R. A., Jones, J. E., Nebert, D. W. Kimura, S. (1989). Human CYP1A2: sequence, gene structure, comparison with the mouse and rat orthologous gene, and differences in liver 1A2 mRNA expression. Mol Endocrinol 3:1399–1408.
  • Ilett, K. F., Castleden, W. M., Vandongen, Y. K., Stacey, M. C., Butler, M. A. Kadlubar, F. F. (1993). Acetylation phenotype and cytochrome P450IA2 phenotype are unlikely to be associated with peripheral arterial disease. Clin Pharmacol Ther 54:317–322.
  • Imai, J., Ieiri, I., Mamiya, K., Miyahara, S., Furuumi, H., Nanba, E., Yamane, M., Fukumaki, Y., Ninomiya, H., Tashiro, N., Otsubo, K. Higuchi, S. (2000). Polymorphism of the cytochrome P450 (CYP) 2C9 gene in Japanese epileptic patients: genetic analysis of the CYP2C9 locus. Pharmacogenetics 10:85–89.
  • Imai, T., Taketani, M., Suzu, T., Kusube, K. Otagiri, M. (1999). In vitro identification of the human cytochrome P-450 enzymes involved in the N-demethylation of azelastine. Drug Metab Dispos 27:942–946.
  • Imaoka, S., Enomoto, K., Oda, Y., Asada, A., Fujimori, M., Shimada, T., Fujita, S., Guengerich, F. P. Funae, Y. (1990). Lidocaine metabolism by human cytochrome P-450s purified from hepatic microsomes: comparison of those with rat hepatic cytochrome P-450s. J Pharmacol Exp Ther 255:1385–1391.
  • Inaba, T., Mizuno, M., Kawai, K., Yokota, K., Oguma, K., Miyoshi, M., Take, S., Okada, H. Tsuji, T. (2002). Randomized, open trial for comparison of proton pump inhibitors in triple therapy for Helicobacter pylori infection in relation to CYP2C19 genotype. J Gastroenterol Hepatol 17:748–753.
  • Ingelman-Sundberg, M. (2005). Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences, evolutionary aspects, and functional diversity. Pharmacogenomics J 5:6–13.
  • Ingelman-Sundberg, M., Sim, S. C., Gomez, A. Rodriguez-Antona, C. (2007). Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic, and clinical aspects. Pharmacol Ther 116:496–526.
  • Ingelman-Sundberg, M., Sim, S. C. Nebert, D. W. (2006). Coffee, myocardial infarction, and CYP nomenclature. JAMA 296:764–765.
  • Inomata, S., Nagashima, A., Itagaki, F., Homma, M., Nishimura, M., Osaka, Y., Okuyama, K., Tanaka, E., Nakamura, T., Kohda, Y., Naito, S., Miyabe, M. Toyooka, H. (2005). CYP2C19 genotype affects diazepam pharmacokinetics and emergence from general anesthesia. Clin Pharmacol Ther 78:647–655.
  • Inoue, K., Yamazaki, H. Shimada, T. (2000). CYP2A6 genetic polymorphisms and liver microsomal coumarin and nicotine oxidation activities in Japanese and Caucasians. Arch Toxicol 73:532–539.
  • Iohom, G., Ni Chonghaile, M., O’Brien, J. K., Cunningham, A. J., Fitzgerald, D. F. Shields, D. C. (2007). An investigation of potential genetic determinants of propofol requirements and recovery from anaesthesia. Eur J Anaesthesiol 24:912–919.
  • Iscan, M., Rostami, H., Iscan, M., Guray, T., Pelkonen, O. Rautio, A. (1994). Interindividual variability of coumarin 7-hydroxylation in a Turkish population. Eur J Clin Pharmacol 47:315–318.
  • Ishibe, N., Wiencke, J. K., Zuo, Z. F., McMillan, A., Spitz, M. Kelsey, K. T. (1997). Susceptibility to lung cancer in light smokers associated with CYP1A1 polymorphisms in Mexican- and African-Americans. Cancer Epidemiol Biomarkers Prev 6:1075–1080.
  • Ishiguro, A., Kubota, T., Ishikawa, H. Iga, T. (2004a). Metabolic activity of dextromethorphan O-demethylation in healthy Japanese volunteers carrying duplicated CYP2D6 genes: duplicated allele of CYP2D6*10 does not increase CYP2D6 metabolic activity. Clin Chim Acta 344:201–204.
  • Ishiguro, A., Kubota, T., Sasaki, H. Iga, T. (2004b). A long PCR assay to distinguish CYP2D6*5 and a novel CYP2D6 mutant allele associated with an 11-kb EcoRI haplotype. Clin Chim Acta 347:217–221.
  • Ishikawa, C., Ozaki, H., Nakajima, T., Ishii, T., Kanai, S., Anjo, S., Shirai, K. Inoue, I. (2004). A frameshift variant of CYP2C8 was identified in a patient who suffered from rhabdomyolysis after administration of cerivastatin. J Hum Genet 49:582–585.
  • Ishizaki, T., Chiba, K., Manabe, K., Koyama, E., Hayashi, M., Yasuda, S., Horai, Y., Tomono, Y., Yamato, C. Toyoki, T. (1995). Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4’-hydroxylation. Clin Pharmacol Ther 58:155–164.
  • Ishizaki, T. Horai, Y. (1999). Review article: cytochrome P450 and the metabolism of proton pump inhibitors—emphasis on rabeprazole. Aliment Pharmacol Ther 13(Suppl 3):27–36.
  • Isomoto, H., Inoue, K., Furusu, H., Enjoji, A., Fujimoto, C., Yamakawa, M., Hirakata, Y., Omagari, K., Mizuta, Y., Murase, K., Shimada, S., Murata, I. Kohno, S. (2003). High-dose rabeprazole-amoxicillin versus rabeprazole-amoxicillin-metronidazole as second-line treatment after failure of the Japanese standard regimen for Helicobacter pylori infection. Aliment Pharmacol Ther 18:101–107.
  • Iwashima, K., Yasui-Furukori, N., Kaneda, A., Saito, M., Nakagami, T., Sato, Y. Kaneko, S. (2007). No association between CYP2D6 polymorphisms and personality trait in Japanese. Br J Clin Pharmacol 64:96–99.
  • Jaakkola, T., Backman, J. T., Neuvonen, M., Laitila, J. Neuvonen, P. J. (2006a). Effect of rifampicin on the pharmacokinetics of pioglitazone. Br J Clin Pharmacol 61:70–78.
  • Jaakkola, T., Backman, J. T., Neuvonen, M. Neuvonen, P. J. (2005). Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther 77:404–414.
  • Jaakkola, T., Laitila, J., Neuvonen, P. J. Backman, J. T. (2006b). Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol 99:44–51.
  • Jack, M. L. Colburn, W. A. (1983). Pharmacokinetic model for diazepam and its major metabolite desmethyldiazepam following diazepam administration. J Pharm Sci 72:1318–1323.
  • Jackson, P. E. Groopman, J. D. (1999). Aflatoxin and liver cancer. Baillieres Best Pract Res Clin Gastroenterol 13:545–555.
  • Jacob, R. M., Johnstone, E. C., Neville, M. J. Walton, R. T. (2004). Identification of CYP2B6 sequence variants by use of multiplex PCR with allele-specific genotyping. Clin Chem 50:1372–1377.
  • Jacobsen, W., Kuhn, B., Soldner, A., Kirchner, G., Sewing, K. F., Kollman, P. A., Benet, L. Z. Christians, U. (2000). Lactonization is the critical first step in the disposition of the 3-hydroxy- 3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos 28:1369–1378.
  • Jacobson, P. A., Green, K., Birnbaum, A. Remmel, R. P. (2002). Cytochrome P450 isozymes 3A4 and 2B6 are involved in the in vitro human metabolism of thiotepa to TEPA. Cancer Chemother Pharmacol 49:461–467.
  • Jacolot, F., Simon, I., Dreano, Y., Beaune, P., Riche, C. Berthou, F. (1991). Identification of the cytochrome P450 IIIA family as the enzymes involved in the N-demethylation of tamoxifen in human liver microsomes. Biochem Pharmacol 41:1911–1919.
  • Jacqz-Aigrain, E., Funck-Brentano, C. Cresteil, T. (1993). CYP2D6- and CYP3A-dependent metabolism of dextromethorphan in humans. Pharmacogenetics 3:197–204.
  • Jaiswal, A. K., Gonzalez, F. J. Nebert, D. W. (1985). Human dioxin-inducible cytochrome P1-450: complementary DNA and amino acid sequence. Science 228:80–83.
  • Jaiswal, A. K., Nebert, D. W., McBride, O. W. Gonzalez, F. J. (1987). Human P(3)450: cDNA and complete protein sequence, repetitive Alu sequences in the 3’ nontranslated region, and localization of gene to chromosome 15. J Exp Pathol 3:1–17.
  • Jajoo, H. K., Mayol, R. F., LaBudde, J. A. Blair, I. A. (1990). Structural characterization of urinary metabolites of the antiarrhythmic drug encainide in human subjects. Drug Metab Dispos 18:28–35.
  • Jakubowski, J. A., Winters, K. J., Naganuma, H. Wallentin, L. (2007). Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev 25:357–374.
  • Jalas, J. R., Ding, X. Murphy, S. E. (2003). Comparative metabolism of the tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol by rat cytochrome P450 2A3 and human cytochrome P450 2A13. Drug Metab Dispos 31:1199–1202.
  • Jann, M. W., Shirley, K. L. Small, G. W. (2002). Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors. Clin Pharmacokinet 41:719–739.
  • Jansing, R. L., Chao, E. S. Kaminsky, L. S. (1992). Phase II metabolism of warfarin in primary culture of adult rat hepatocytes. Mol Pharmacol 41:209–215.
  • Jaruratanasirikul, S. Hortiwakul, R. (1994). The inhibitory effect of amiodarone and desethylamiodarone on dextromethorphan O-demethylation in human and rat liver microsomes. J Pharm Pharmacol 46:933–935.
  • Jaruratanasirikul, S. Sriwiriyajan, S. (2007). Pharmacokinetic study of the interaction between itraconazole and nevirapine. Eur J Clin Pharmacol 63:451–456.
  • Jarvis, B. Coukell, A. J. (1998). Mexiletine. A review of its therapeutic use in painful diabetic neuropathy. Drugs 56:691–707.
  • Jarvis, B. Simpson, K. (2000). Clopidogrel: a review of its use in the prevention of atherothrombosis. Drugs 60:347–377.
  • Jauch, R., Kopitar, Z., Prox, A. Zimmer, A. (1976). [Pharmacokinetics and metabolism of trazodone in man (author’s transl)]. Arzneimittelforschung 26:2084–2089.
  • Jazwinska-Tarnawska, E., Orzechowska-Juzwenko, K., Niewinski, P., Rzemislawska, Z., Loboz-Grudzien, K., Dmochowska-Perz, M. Slawin, J. (2001). The influence of CYP2D6 polymorphism on the antiarrhythmic efficacy of propafenone in patients with paroxysmal atrial fibrillation during 3 months propafenone prophylactic treatment. Int J Clin Pharmacol Ther 39:288–292.
  • Jenner, P. (2003). The contribution of the MPTP-treated primate model to the development of new treatment strategies for Parkinson’s disease. Parkinsonism Relat Disord 9:131–137.
  • Jerling, M., Dahl, M. L., Aberg-Wistedt, A., Liljenberg, B., Landell, N. E., Bertilsson, L. Sjoqvist, F. (1996). The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol. Clin Pharmacol Ther 59:423–428.
  • Ji, L., Pan, S., Marti-Jaun, J., Hanseler, E., Rentsch, K. Hersberger, M. (2002). Single-step assays to analyze CYP2D6 gene polymorphisms in Asians: allele frequencies and a novel *14B allele in mainland Chinese. Clin Chem 48:983–988.
  • Jiang, J. H., Jia, W. H., Chen, H. K., Feng, B. J., Qin, H. D., Pan, Z. G., Shen, G. P., Huang, L. X., Feng, Q. S., Chen, L. Z., Lin, D. X. Zeng, Y. X. (2004). Genetic polymorphisms of CYP2A13 and its relationship to nasopharyngeal carcinoma in the Cantonese population. J Transl Med 2:24.
  • Jiang, Z. P., Shu, Y., Chen, X. P., Huang, S. L., Zhu, R. H., Wang, W., He, N. Zhou, H. H. (2002). The role of CYP2C19 in amitriptyline N-demethylation in Chinese subjects. Eur J Clin Pharmacol 58:109–113.
  • Jiko, M., Yano, I., Sato, E., Takahashi, K., Motohashi, H., Masuda, S., Okuda, M., Ito, N., Nakamura, E., Segawa, T., Kamoto, T., Ogawa, O. Inui, K. (2007). Pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine, and effects of CYP3A5 and MDR1 polymorphisms in patients with urogenital cancers. Int J Clin Oncol 12:284–290.
  • Jimenez-Jimenez, F. J., Tabernero, C., Mena, M. A., Garcia de Yebenes, J., Garcia de Yebenes, M. J., Casarejos, M. J., Pardo, B., Garcia-Agundez, J. A., Benitez, J., Martinez, A. et al. (1991). Acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in a model of rat designated a poor metabolizer of debrisoquine. J Neurochem 57:81–87.
  • Jin, Y., Desta, Z., Stearns, V., Ward, B., Ho, H., Lee, K. H., Skaar, T., Storniolo, A. M., Li, L., Araba, A., Blanchard, R., Nguyen, A., Ullmer, L., Hayden, J., Lemler, S., Weinshilboum, R. M., Rae, J. M., Hayes, D. F. Flockhart, D. A. (2005). CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 97:30–39.
  • Jinno, H., Tanaka-Kagawa, T., Ohno, A., Makino, Y., Matsushima, E., Hanioka, N. Ando, M. (2003). Functional characterization of cytochrome P450 2B6 allelic variants. Drug Metab Dispos 31:398–403.
  • Johansen, O. E. Birkeland, K. I. (2007). Defining the role of repaglinide in the management of type 2 diabetes mellitus: a review. Am J Cardiovasc Drugs 7:319–335.
  • Johansson, I., Lundqvist, E., Bertilsson, L., Dahl, M. L., Sjoqvist, F. Ingelman-Sundberg, M. (1993). Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci U S A 90:11825–11829.
  • Johansson, I., Oscarson, M., Yue, Q. Y., Bertilsson, L., Sjoqvist, F. Ingelman-Sundberg, M. (1994). Genetic analysis of the Chinese cytochrome P4502D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol 46:452–459.
  • Johnson, J. A. Burlew, B. S. (1996). Metoprolol metabolism via cytochrome P4502D6 in ethnic populations. Drug Metab Dispos 24:350–355.
  • Johnson, J. A., Herring, V. L., Wolfe, M. S. Relling, M. V. (2000). CYP1A2 and CYP2D6 4-hydroxylate propranolol and both reactions exhibit racial differences. J Pharmacol Exp Ther 294:1099–1105.
  • Johnson, M. D., Zuo, H., Lee, K. H., Trebley, J. P., Rae, J. M., Weatherman, R. V., Desta, Z., Flockhart, D. A. Skaar, T. C. (2004). Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 85:151–159.
  • Johnston, S. R., Gumbrell, L. A., Evans, T. R., Coleman, R. E., Smith, I. E., Twelves, C. J., Soukop, M., Rea, D. W., Earl, H. M., Howell, A., Jones, A., Canney, P., Powles, T. J., Haynes, B. P., Nutley, B., Grimshaw, R., Jarman, M., Halbert, G. W., Brampton, M., Haviland, J., Dowsett, M. Coombes, R. C. (2004). A cancer research (UK) randomized phase II study of idoxifene in patients with locally advanced/metastatic breast cancer resistant to tamoxifen. Cancer Chemother Pharmacol 53:341–348.
  • Jones, B. C., Hyland, R., Ackland, M., Tyman, C. A. Smith, D. A. (1998). Interaction of terfenadine and its primary metabolites with cytochrome P450 2D6. Drug Metab Dispos 26:875–882.
  • Jones, R. M. Lim, C. K. (2002). Toremifene metabolism in rat, mouse, and human liver microsomes: identification of alpha-hydroxytoremifene by LC-MS. Biomed Chromatogr 16:361–363.
  • Jordan, V. C. (1982). Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Breast Cancer Res Treat 2:123–138.
  • Jordan, V. C. (2007). Chemoprevention of breast cancer with selective oestrogen-receptor modulators. Nat Rev Cancer 7:46–53.
  • Jordan, V. C., Collins, M. M., Rowsby, L. Prestwich, G. (1977). A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J Endocrinol 75:305–316.
  • Jordan, V. C. O’Malley, B. W. (2007). Selective estrogen-receptor modulators and antihormonal resistance in breast cancer. J Clin Oncol 25:5815–5824.
  • Jorenby, D. E., Leischow, S. J., Nides, M. A., Rennard, S. I., Johnston, J. A., Hughes, A. R., Smith, S. S., Muramoto, M. L., Daughton, D. M., Doan, K., Fiore, M. C. Baker, T. B. (1999). A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med 340:685–691.
  • Josephson, F., Allqvist, A., Janabi, M., Sayi, J., Aklillu, E., Jande, M., Mahindi, M., Burhenne, J., Bottiger, Y., Gustafsson, L. L., Haefeli, W. E. Bertilsson, L. (2007). CYP3A5 genotype has an impact on the metabolism of the HIV protease inhibitor saquinavir. Clin Pharmacol Ther 81:708–712.
  • Jounaidi, Y., Hyrailles, V., Gervot, L. Maurel, P. (1996). Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein? Biochem Biophys Res Commun 221:466–470.
  • Judge, H. M., Buckland, R. J., Sugidachi, A., Jakubowski, J. A. Storey, R. F. (2008). The active metabolite of prasugrel effectively blocks the platelet P2Y12 receptor and inhibits procoagulant and pro-inflammatory platelet responses. Platelets 19:125–133.
  • Jung, F., Richardson, T. H., Raucy, J. L. Johnson, E. F. (1997). Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P4502C18 and P4502C19 as low K(M) diazepam N-demethylases. Drug Metab Dispos 25:133–139.
  • Jung, S. M., Kim, K. A., Cho, H. K., Jung, I. G., Park, P. W., Byun, W. T. Park, J. Y. (2005). Cytochrome P450 3A inhibitor itraconazole affects plasma concentrations of risperidone and 9-hydroxyrisperidone in schizophrenic patients. Clin Pharmacol Ther 78:520–528.
  • Jungnickel, P. W. (2000). Pantoprazole: a new proton pump inhibitor. Clin Ther 22:1268–1293.
  • Justenhoven, C., Hamann, U., Schubert, F., Zapatka, M., Pierl, C. B., Rabstein, S., Selinski, S., Mueller, T., Ickstadt, K., Gilbert, M., Ko, Y. D., Baisch, C., Pesch, B., Harth, V., Bolt, H. M., Vollmert, C., Illig, T., Eils, R., Dippon, J. Brauch, H. (2008). Breast cancer: a candidate gene approach across the estrogen metabolic pathway. Breast Cancer Res Treat 108:137–149.
  • Justo, D., Prokhorov, V., Heller, K. Zeltser, D. (2005). Torsade de pointes induced by psychotropic drugs and the prevalence of its risk factors. Acta Psychiatr Scand 111:171–176.
  • Kadlubar, F. F., Berkowitz, G. S., Delongchamp, R. R., Wang, C., Green, B. L., Tang, G., Lamba, J., Schuetz, E. Wolff, M. S. (2003). The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer. Cancer Epidemiol Biomarkers Prev 12:327–331.
  • Kaduszkiewicz, H., Zimmermann, T., Beck-Bornholdt, H. P. van den Bussche, H. (2005). Cholinesterase inhibitors for patients with Alzheimer’s disease: systematic review of randomised clinical trials. BMJ 331:321–327.
  • Kagimoto, M., Heim, M., Kagimoto, K., Zeugin, T. Meyer, U. A. (1990). Multiple mutations of the human cytochrome P450IID6 gene (CYP2D6) in poor metabolizers of debrisoquine. Study of the functional significance of individual mutations by expression of chimeric genes. J Biol Chem 265:17209–17214.
  • Kahn, R. S. Wetzler, S. (1991). m-chlorophenylpiperazine as a probe of serotonin function. Biol Psychiatry 30:1139–1166.
  • Kaiser, R., Sezer, O., Papies, A., Bauer, S., Schelenz, C., Tremblay, P. B., Possinger, K., Roots, I. Brockmoller, J. (2002). Patient-tailored antiemetic treatment with 5-hydroxytryptamine type 3 receptor antagonists according to cytochrome P-450 2D6 genotypes. J Clin Oncol 20:2805–2811.
  • Kaivosaari, S., Toivonen, P., Hesse, L. M., Koskinen, M., Court, M. H. Finel, M. (2007). Nicotine glucuronidation and the human UDP-glucuronosyltransferase UGT2B10. Mol Pharmacol 72:761–768.
  • Kajosaari, L. I., Jaakkola, T., Neuvonen, P. J. Backman, J. T. (2006). Pioglitazone, an in vitro inhibitor of CYP2C8 and CYP3A4, does not increase the plasma concentrations of the CYP2C8 and CYP3A4 substrate repaglinide. Eur J Clin Pharmacol 62:217–223.
  • Kajosaari, L. I., Laitila, J., Neuvonen, P. J. Backman, J. T. (2005). Metabolism of repaglinide by CYP2C8 and CYP3A4 in vitro: effect of fibrates and rifampicin. Basic Clin Pharmacol Toxicol 97:249–256.
  • Kaku, T., Ogura, K., Nishiyama, T., Ohnuma, T., Muro, K. Hiratsuka, A. (2004). Quaternary ammonium-linked glucuronidation of tamoxifen by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem Pharmacol 67: 2093–2102.
  • Kale, P. Johnson, L. B. (2005). Second-generation azole antifungal agents. Drugs Today (Barc) 41:91–105.
  • Kalgutkar, A. S., Nguyen, H. T., Vaz, A. D., Doan, A., Dalvie, D. K., McLeod, D. G. Murray, J. C. (2003a). In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active alpha-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes. Drug Metab Dispos 31:1240–1250.
  • Kalgutkar, A. S., Zhou, S., Fahmi, O. A. Taylor, T. J. (2003b). Influence of lipophilicity on the interactions of N-alkyl-4-phenyl-1,2,3,6-tetrahydropyridines and their positively charged N-alkyl-4-phenylpyridinium metabolites with cytochrome P450 2D6. Drug Metab Dispos 31:596–605.
  • Kall, M. A. Clausen, J. (1995). Dietary effect on mixed function P450 1A2 activity assayed by estimation of caffeine metabolism in man. Hum Exp Toxicol 14:801–807.
  • Kalliokoski, A., Neuvonen, M., Neuvonen, P. J. Niemi, M. (2008). Different effects of SLCO1B1 polymorphism on the pharmacokinetics and pharmacodynamics of repaglinide and nateglinide. J Clin Pharmacol 48:311–321.
  • Kam, P. C. Nethery, C. M. (2003). The thienopyridine derivatives (platelet adenosine diphosphate receptor antagonists), pharmacology and clinical developments. Anaesthesia 58:28–35.
  • Kamada, T., Chow, T., Hiroi, T., Imaoka, S., Morimoto, K., Ohde, H. Funae, Y. (2002). Metabolism of selegiline hydrochloride, a selective monoamine b-type inhibitor, in human liver microsomes. Drug Metab Pharmacokinet 17:199–206.
  • Kamali, F. Pirohamed, M. (2006). The future prospects of pharmacogenetics in oral anticoagulation therapy. Br J Clin Pharmacol 61:746–751.
  • Kaminsky, L. S. Zhang, Z. Y. (1997). Human P450 metabolism of warfarin. Pharmacol Ther 73:67–74.
  • Kammerer, R. C. Lampe, M. A. (1987). In vitro metabolism of chlorpheniramine in the rabbit. Biochem Pharmacol 36:3445–3452.
  • Kaneko, A., Bergqvist, Y., Takechi, M., Kalkoa, M., Kaneko, O., Kobayakawa, T., Ishizaki, T. Bjorkman, A. (1999a). Intrinsic efficacy of proguanil against falciparum and vivax malaria independent of the metabolite cycloguanil. J Infect Dis 179:974–979.
  • Kaneko, A., Bergqvist, Y., Taleo, G., Kobayakawa, T., Ishizaki, T. Bjorkman, A. (1999b). Proguanil disposition and toxicity in malaria patients from Vanuatu with high frequencies of CYP2C19 mutations. Pharmacogenetics 9:317–326.
  • Kaneko, A., Kaneko, O., Taleo, G., Bjorkman, A. Kobayakawa, T. (1997). High frequencies of CYP2C19 mutations and poor metabolism of proguanil in Vanuatu. Lancet 349:921–922.
  • Kang, Y., Park, S., Yim, C., Kwak, H., Gajendrarao, P., Krishnamoorthy, N., Yun, S. C., Lee, K. Han, K. (2009). The CYP3A4*18 genotype in the cytochrome P450 3A4 gene, a rapid metabolizer of sex steroids, is associated with low bone mineral density. Clin Pharmacol Ther 85:312–318.
  • Kantola, T., Backman, J. T., Niemi, M., Kivisto, K. T. Neuvonen, P. J. (2000). Effect of fluconazole on plasma fluvastatin and pravastatin concentrations. Eur J Clin Pharmacol 56:225–229.
  • Kappelhoff, B. S., van Leth, F., MacGregor, T. R., Lange, J., Beijnen, J. H. Huitema, A. D. (2005). Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study. Antivir Ther 10:145–155.
  • Kariya, S., Isozaki, S., Uchino, K., Suzuki, T. Narimatsu, S. (1996). Oxidative metabolism of flunarizine and cinnarizine by microsomes from B-lymphoblastoid cell lines expressing human cytochrome P450 enzymes. Biol Pharm Bull 19:1511–1514.
  • Kato, R., Yamazoe, Y. Yasumori, T. (1990). Pharmacogenetics and polymorphism of human P-450 which activates and detoxicates xenobiotics and carcinogens. Princess Takamatsu Symp 21:45–53.
  • Katsuki, H., Hamada, A., Nakamura, C., Arimori, K. Nakano, M. (2001). Role of CYP3A4 and CYP2C19 in the stereoselective metabolism of lansoprazole by human liver microsomes. Eur J Clin Pharmacol 57:709–715.
  • Katz, M. R. (1991). Raised serum levels of desipramine with the antiarrhythmic propafenone. J Clin Psychiatry 52:432–433.
  • Katzenellenbogen, B. S., Norman, M. J., Eckert, R. L., Peltz, S. W. Mangel, W. F. (1984). Bioactivities, estrogen receptor interactions, and plasminogen activator-inducing activities of tamoxifen and hydroxy-tamoxifen isomers in MCF-7 human breast cancer cells. Cancer Res 44:112–119.
  • Kaukonen, K. M., Olkkola, K. T. Neuvonen, P. J. (1998). Fluconazole but not itraconazole decreases the metabolism of losartan to E-3174. Eur J Clin Pharmacol 53:445–449.
  • Kavirajan, H. Schneider, L. S. (2007). Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: a meta-analysis of randomised, controlled trials. Lancet Neurol 6:782–792.
  • Kawabata, H., Habu, Y., Tomioka, H., Kutsumi, H., Kobayashi, M., Oyasu, K., Hayakumo, T., Mizuno, S., Kiyota, K., Nakajima, M., Kimoto, K., Inokuchi, H. Kawai, K. (2003). Effect of different proton pump inhibitors, differences in CYP2C19 genotype, and antibiotic resistance on the eradication rate of Helicobacter pylori infection by a 1-week regimen of proton pump inhibitor, amoxicillin, and clarithromycin. Aliment Pharmacol Ther 17:259–264.
  • Kawai, K., Kawasaki-Tokui, Y., Odaka, T., Tsuruta, F., Kazui, M., Iwabuchi, H., Nakamura, T., Kinoshita, T., Ikeda, T., Yoshioka, T., Komai, T. Nakamura, K. (1997). Disposition and metabolism of the new oral antidiabetic drug troglitazone in rats, mice, and dogs. Arzneimittelforschung 47:356–368.
  • Kawajiri, K., Eguchi, H., Nakachi, K., Sekiya, T. Yamamoto, M. (1996). Association of CYP1A1 germ line polymorphisms with mutations of the p53 gene in lung cancer. Cancer Res 56:72–76.
  • Kawajiri, K., Nakachi, K., Imai, K., Yoshii, A., Shinoda, N. Watanabe, J. (1990a). Identification of genetically high risk individuals to lung cancer by DNA polymorphism of the cytochrome P450IA1 gene. FEBS Lett 263:131–133.
  • Kawajiri, K., Nakachi, K., Imai, K., Yoshii, A., Shinoda, N. Watanabe, J. (1990b). Identification of genetically high risk individuals to lung cancer by DNA polymorphisms of the cytochrome P450IA1 gene. FEBS Lett 263:131–133.
  • Kawajiri, K., Watanabe, J., Eguchi, H. Hayashi, S. (1995). Genetic polymorphisms of drug-metabolizing enzymes and lung cancer susceptibility. Pharmacogenetics 5 Spec No:S70–S73.
  • Kawamura, M., Ohara, S., Koike, T., Iijima, K., Suzuki, J., Kayaba, S., Noguchi, K., Hamada, S., Noguchi, M. Shimosegawa, T. (2003). The effects of lansoprazole on erosive reflux oesophagitis are influenced by CYP2C19 polymorphism. Aliment Pharmacol Ther 17:965–973.
  • Kawashima, H. Strobel, H. W. (1995). cDNA cloning of three new forms of rat brain cytochrome P450 belonging to the CYP4F subfamily. Biochem Biophys Res Commun 217:1137–1144.
  • Kazierad, D. J., Martin, D. E., Blum, R. A., Tenero, D. M., Ilson, B., Boike, S. C., Etheredge, R. Jorkasky, D. K. (1997). Effect of fluconazole on the pharmacokinetics of eprosartan and losartan in healthy male volunteers. Clin Pharmacol Ther 62:417–425.
  • Keegan, P. Loughman, B. E. (2001). Early clinical trials of chemopreventive and biologic agents: designs, populations, and endpoints. Urology 57:216–219.
  • Keizers, P. H., Lussenburg, B. M., de Graaf, C., Mentink, L. M., Vermeulen, N. P. Commandeur, J. N. (2004). Influence of phenylalanine 120 on cytochrome P450 2D6 catalytic selectivity and regiospecificity: crucial role in 7-methoxy-4-(aminomethyl)-coumarin metabolism. Biochem Pharmacol 68:2263–2271.
  • Kerb, R., Aynacioglu, A. S., Brockmoller, J., Schlagenhaufer, R., Bauer, S., Szekeres, T., Hamwi, A., Fritzer-Szekeres, M., Baumgartner, C., Ongen, H. Z., Guzelbey, P., Roots, I. Brinkmann, U. (2001). The predictive value of MDR1, CYP2C9, and CYP2C19 polymorphisms for phenytoin plasma levels. Pharmacogenomics J 1:204–210.
  • Khanna, S., John, J. P. Reddy, L. P. (2001). Neuroendocrine and behavioral responses to mCPP in obsessive-compulsive disorder. Psychoneuroendocrinology 26:209–223.
  • Kharasch, E. D., Hoffer, C., Whittington, D. Sheffels, P. (2004). Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther 76:250–269.
  • Kharasch, E. D., Mitchell, D. Coles, R. (2008). Stereoselective bupropion hydroxylation as an in vivo phenotypic probe for cytochrome P4502B6 (CYP2B6) activity. J Clin Pharmacol 48:464–474.
  • Kiang, T. K., Ho, P. C., Anari, M. R., Tong, V., Abbott, F. S. Chang, T. K. (2006). Contribution of CYP2C9, CYP2A6, and CYP2B6 to valproic acid metabolism in hepatic microsomes from individuals with the CYP2C9*1/*1 genotype. Toxicol Sci 94:261–271.
  • Kidd, R. S., Curry, T. B., Gallagher, S., Edeki, T., Blaisdell, J. Goldstein, J. A. (2001). Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. Pharmacogenetics 11:803–808.
  • Kidd, R. S., Straughn, A. B., Meyer, M. C., Blaisdell, J., Goldstein, J. A. Dalton, J. T. (1999). Pharmacokinetics of chlorpheniramine, phenytoin, glipizide, and nifedipine in an individual homozygous for the CYP2C9*3 allele. Pharmacogenetics 9:71–80.
  • Kilicarslan, T., Haining, R. L., Rettie, A. E., Busto, U., Tyndale, R. F. Sellers, E. M. (2001). Flunitrazepam metabolism by cytochrome P450S 2C19 and 3A4. Drug Metab Dispos 29:460–465.
  • Kim, D., Wu, Z. L. Guengerich, F. P. (2005a). Analysis of coumarin 7-hydroxylation activity of cytochrome P450 2A6 using random mutagenesis. J Biol Chem 280:40319–40327.
  • Kim, J. R., Seo, H. B., Cho, J. Y., Kang, D. H., Kim, Y. K., Bahk, W. M., Yu, K. S., Shin, S. G., Kwon, J. S. Jang, I. J. (2008). Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients. Br J Clin Pharmacol 66:802–810.
  • Kim, K. A., Chung, J., Jung, D. H. Park, J. Y. (2004). Identification of cytochrome P450 isoforms involved in the metabolism of loperamide in human liver microsomes. Eur J Clin Pharmacol 60:575–581.
  • Kim, K. A., Kim, M. J., Park, J. Y., Shon, J. H., Yoon, Y. R., Lee, S. S., Liu, K. H., Chun, J. H., Hyun, M. H. Shin, J. G. (2003a). Stereoselective metabolism of lansoprazole by human liver cytochrome P450 enzymes. Drug Metab Dispos 31:1227–1234.
  • Kim, K. A., Park, J. Y., Lee, J. S. Lim, S. (2003b). Cytochrome P450 2C8 and CYP3A4/5 are involved in chloroquine metabolism in human liver microsomes. Arch Pharm Res 26:631–637.
  • Kim, K. A., Shon, J. H., Park, J. Y., Yoon, Y. R., Kim, M. J., Yun, D. H., Kim, M. K., Cha, I. J., Hyun, M. H. Shin, J. G. (2002). Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19. Clin Pharmacol Ther 72:90–99.
  • Kim, M., Shen, D. D., Eddy, A. C., Nelson, W. L. Roskos, L. K. (1993). Inhibition of the enantioselective oxidative metabolism of metoprolol by verapamil in human liver microsomes. Drug Metab Dispos 21:309–317.
  • Kim, M. K., Cho, J. Y., Lim, H. S., Hong, K. S., Chung, J. Y., Bae, K. S., Oh, D. S., Shin, S. G., Lee, S. H., Lee, D. H., Min, B. Jang, I. J. (2003c). Effect of the CYP2D6 genotype on the pharmacokinetics of tropisetron in healthy Korean subjects. Eur J Clin Pharmacol 59:111–116.
  • Kim, S. Y., Laxmi, Y. R., Suzuki, N., Ogura, K., Watabe, T., Duffel, M. W. Shibutani, S. (2005b). Formation of tamoxifen-DNA adducts via O-sulfonation, not O-acetylation, of alpha-hydroxytamoxifen in rat and human livers. Drug Metab Dispos 33:1673–1678.
  • Kimber-Trojnar, Z., Marciniak, B., Leszczynska-Gorzelak, B., Trojnar, M. Oleszczuk, J. (2008). Glyburide for the treatment of gestational diabetes mellitus. Pharmacol Rep 60:308–318.
  • Kimura, S., Umeno, M., Skoda, R. C., Meyer, U. A. Gonzalez, F. J. (1989). The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. Am J Hum Genet 45:889–904.
  • King, B. P., Khan, T. I., Aithal, G. P., Kamali, F. Daly, A. K. (2004). Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism. Pharmacogenetics 14:813–822.
  • King, C., Finley, B. Franklin, R. (2000). The glucuronidation of morphine by dog liver microsomes: identification of morphine-6-O-glucuronide. Drug Metab Dispos 28:661–663.
  • King, L. M., Gainer, J. V., David, G. L., Dai, D., Goldstein, J. A., Brown, N. J. Zeldin, D. C. (2005). Single-nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharmacogenet Genomics 15:7–13.
  • Kirby, G. M., Wolf, C. R., Neal, G. E., Judah, D. J., Henderson, C. J., Srivatanakul, P. Wild, C. P. (1993). In vitro metabolism of aflatoxin B1 by normal and tumorous liver tissue from Thailand. Carcinogenesis 14:2613–2620.
  • Kirchheiner, J. (2008). CYP2D6 phenotype prediction from genotype: which system is the best? Clin Pharmacol Ther 83:225–227.
  • Kirchheiner, J., Bauer, S., Meineke, I., Rohde, W., Prang, V., Meisel, C., Roots, I. Brockmoller, J. (2002a). Impact of CYP2C9 and CYP2C19 polymorphisms on tolbutamide kinetics and the insulin and glucose response in healthy volunteers. Pharmacogenetics 12:101–109.
  • Kirchheiner, J., Brockmoller, J., Meineke, I., Bauer, S., Rohde, W., Meisel, C. Roots, I. (2002b). Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers. Clin Pharmacol Ther 71:286–296.
  • Kirchheiner, J., Heesch, C., Bauer, S., Meisel, C., Seringer, A., Goldammer, M., Tzvetkov, M., Meineke, I., Roots, I. Brockmoller, J. (2004a). Impact of the ultrarapid metabolizer genotype of cytochrome P450 2D6 on metoprolol pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 76:302–312.
  • Kirchheiner, J., Keulen, J. T., Bauer, S., Roots, I. Brockmoller, J. (2008a). Effects of the CYP2D6 gene duplication on the pharmacokinetics and pharmacodynamics of tramadol. J Clin Psychopharmacol 28:78–83.
  • Kirchheiner, J., Klein, C., Meineke, I., Sasse, J., Zanger, U. M., Murdter, T. E., Roots, I. Brockmoller, J. (2003a). Bupropion and 4-OH-bupropion pharmacokinetics in relation to genetic polymorphisms in CYP2B6. Pharmacogenetics 13:619–626.
  • Kirchheiner, J., Kudlicz, D., Meisel, C., Bauer, S., Meineke, I., Roots, I. Brockmoller, J. (2003b). Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (-)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers. Clin Pharmacol Ther 74:186–194.
  • Kirchheiner, J., Meineke, I., Fuhr, U., Rodriguez-Antona, C., Lebedeva, E. Brockmoller, J. (2008b). Impact of genetic polymorphisms in CYP2C8 and rosiglitazone intake on the urinary excretion of dihydroxyeicosatrienoic acids. Pharmacogenomics 9:277–288.
  • Kirchheiner, J., Meineke, I., Muller, G., Bauer, S., Rohde, W., Meisel, C., Roots, I. Brockmoller, J. (2004b). Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Clin Pharmacokinet 43:267–278.
  • Kirchheiner, J., Meineke, I., Muller, G., Roots, I. Brockmoller, J. (2002c). Contributions of CYP2D6, CYP2C9, and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics 12:571–580.
  • Kirchheiner, J., Meineke, I., Steinbach, N., Meisel, C., Roots, I. Brockmoller, J. (2003c). Pharmacokinetics of diclofenac and inhibition of cyclooxygenases 1 and 2: no relationship to the CYP2C9 genetic polymorphism in humans. Br J Clin Pharmacol 55:51–61.
  • Kirchheiner, J., Muller, G., Meineke, I., Wernecke, K. D., Roots, I. Brockmoller, J. (2003d). Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics. J Clin Psychopharmacol 23:459–466.
  • Kirchheiner, J. Seeringer, A. (2007). Clinical implications of pharmacogenetics of cytochrome P450 drug metabolizing enzymes. Biochim Biophys Acta 1770:489–494.
  • Kirchheiner, J., Stormer, E., Meisel, C., Steinbach, N., Roots, I. Brockmoller, J. (2003e). Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics 13:473–480.
  • Kirchheiner, J., Thomas, S., Bauer, S., Tomalik-Scharte, D., Hering, U., Doroshyenko, O., Jetter, A., Stehle, S., Tsahuridu, M., Meineke, I., Brockmoller, J. Fuhr, U. (2006). Pharmacokinetics and pharmacodynamics of rosiglitazone in relation to CYP2C8 genotype. Clin Pharmacol Ther 80:657–667.
  • Kirkwood, L. C., Nation, R. L. Somogyi, A. A. (1997). Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine. Br J Clin Pharmacol 44:549–555.
  • Kisanga, E. R., Mellgren, G. Lien, E. A. (2005). Excretion of hydroxylated metabolites of tamoxifen in human bile and urine. Anticancer Res 25:4487–4492.
  • Kishimoto, W., Hiroi, T., Sakai, K., Funae, Y. Igarashi, T. (1997). Metabolism of epinastine, a histamine H1 receptor antagonist, in human liver microsomes in comparison with that of terfenadine. Res Commun Mol Pathol Pharmacol 98:273–292.
  • Kishimoto, W., Hiroi, T., Shiraishi, M., Osada, M., Imaoka, S., Kominami, S., Igarashi, T. Funae, Y. (2004). Cytochrome P450 2D catalyze steroid 21-hydroxylation in the brain. Endocrinology 145:699–705.
  • Kisselev, P., Schunck, W. H., Roots, I. Schwarz, D. (2005). Association of CYP1A1 polymorphisms with differential metabolic activation of 17beta-estradiol and estrone. Cancer Res 65:2972–2978.
  • Kitagawa, K., Kunugita, N., Katoh, T., Yang, M. Kawamoto, T. (1999). The significance of the homozygous CYP2A6 deletion on nicotine metabolism: a new genotyping method of CYP2A6 using a single PCR-RFLP. Biochem Biophys Res Commun 262:146–151.
  • Kitagawa, K., Kunugita, N., Kitagawa, M. Kawamoto, T. (2001). CYP2A6*6, a novel polymorphism in cytochrome p450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity. J Biol Chem 276:17830–17835.
  • Kitagawa, M., Ravindernath, A., Suzuki, N., Rieger, R., Terashima, I., Umemoto, A. Shibutani, S. (2000). Identification of tamoxifen-DNA adducts induced by alpha-acetoxy-N-desmethyltamoxifen. Chem Res Toxicol 13:761–769.
  • Kiyotani, K., Fujieda, M., Yamazaki, H., Shimada, T., Guengerich, F. P., Parkinson, A., Nakagawa, K., Ishizaki, T. Kamataki, T. (2002). Twenty-one novel single-nucleotide polymorphisms (SNPs) of the CYP2A6 gene in Japanese and Caucasians. Drug Metab Pharmacokinet 17:482–487.
  • Kiyotani, K., Mushiroda, T., Sasa, M., Bando, Y., Sumitomo, I., Hosono, N., Kubo, M., Nakamura, Y. Zembutsu, H. (2008). Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy. Cancer Sci 99:995–999.
  • Kiyotani, K., Yamazaki, H., Fujieda, M., Iwano, S., Matsumura, K., Satarug, S., Ujjin, P., Shimada, T., Guengerich, F. P., Parkinson, A., Honda, G., Nakagawa, K., Ishizaki, T. Kamataki, T. (2003). Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9). Pharmacogenetics 13:689–695.
  • Klein, A., Sami, M. Selinger, K. (1985). Mexiletine kinetics in healthy subjects taking cimetidine. Clin Pharmacol Ther 37:669–673.
  • Klein, K., Lang, T., Saussele, T., Barbosa-Sicard, E., Schunck, W. H., Eichelbaum, M., Schwab, M. Zanger, U. M. (2005). Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet Genomics 15:861–873.
  • Klein, K., Tatzel, S., Raimundo, S., Saussele, T., Hustert, E., Pleiss, J., Eichelbaum, M. Zanger, U. M. (2007). A natural variant of the heme-binding signature (R441C) resulting in complete loss of function of CYP2D6. Drug Metab Dispos 35:1247–1250.
  • Klose, T. S., Blaisdell, J. A. Goldstein, J. A. (1999). Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs. J Biochem Mol Toxicol 13:289–295.
  • Klotz, U. (2007). Antiarrhythmics: elimination and dosage considerations in hepatic impairment. Clin Pharmacokinet 46:985–996.
  • Knauf, H. Mutschler, E. (1998). Clinical pharmacokinetics and pharmacodynamics of torasemide. Clin Pharmacokinet 34:1–24.
  • Knauf, H., Spahn, H. Mutschler, E. (1991). The loop diuretic torasemide in chronic renal failure. Pharmacokinetics and pharmacodynamics. Drugs 41(Suppl 3):23–34.
  • Knodell, R. G., Dubey, R. K., Wilkinson, G. R. Guengerich, F. P. (1988). Oxidative metabolism of hexobarbital in human liver: relationship to polymorphic S-mephenytoin 4-hydroxylation. J Pharmacol Exp Ther 245:845–849.
  • Ko, J. W., Desta, Z., Soukhova, N. V., Tracy, T. Flockhart, D. A. (2000). In vitro inhibition of the cytochrome P450 (CYP450) system by the antiplatelet drug ticlopidine: potent effect on CYP2C19 and CYP2D6. Br J Clin Pharmacol 49:343–351.
  • Kobari, T., Itoh, T., Hirakawa, T., Namekawa, H., Suzuki, T., Satoh, T., Iida, N., Ohtsu, F. Hayakawa, H. (1984). Dose-dependent pharmacokinetics of aprindine in healthy volunteers. Eur J Clin Pharmacol 26:129–131.
  • Kobayashi, K., Abe, S., Nakajima, M., Shimada, N., Tani, M., Chiba, K. Yamamoto, T. (1999a). Role of human CYP2B6 in S-mephobarbital N-demethylation. Drug Metab Dispos 27:1429–1433.
  • Kobayashi, K., Chiba, K., Yagi, T., Shimada, N., Taniguchi, T., Horie, T., Tani, M., Yamamoto, T., Ishizaki, T. Kuroiwa, Y. (1997). Identification of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes. J Pharmacol Exp Ther 280:927–933.
  • Kobayashi, K., Ishizuka, T., Shimada, N., Yoshimura, Y., Kamijima, K. Chiba, K. (1999b). Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P-450 in vitro. Drug Metab Dispos 27:763–766.
  • Kobayashi, K., Kogo, M., Tani, M., Shimada, N., Ishizaki, T., Numazawa, S., Yoshida, T., Yamamoto, T., Kuroiwa, Y. Chiba, K. (2001). Role of CYP2C19 in stereoselective hydroxylation of mephobarbital by human liver microsomes. Drug Metab Dispos 29:36–40.
  • Kobayashi, K., Morita, J., Chiba, K., Wanibuchi, A., Kimura, M., Irie, S., Urae, A. Ishizaki, T. (2004). Pharmacogenetic roles of CYP2C19 and CYP2B6 in the metabolism of R- and S-mephobarbital in humans. Pharmacogenetics 14:549–556.
  • Komatsu, T., Yamazaki, H., Shimada, N., Nakajima, M. Yokoi, T. (2000). Roles of cytochromes P450 1A2, 2A6, and 2C8 in 5-fluorouracil formation from tegafur, an anticancer prodrug, in human liver microsomes. Drug Metab Dispos 28:1457–1463.
  • Komi, J., Lankinen, K. S., Harkonen, P., DeGregorio, M. W., Voipio, S., Kivinen, S., Tuimala, R., Vihtamaki, T., Vihko, K., Ylikorkala, O. Erkkola, R. (2005). Effects of ospemifene and raloxifene on hormonal status, lipids, genital tract, and tolerability in postmenopausal women. Menopause 12:202–209.
  • Komura, H. Iwaki, M. (2005). Nonlinear pharmacokinetics of propafenone in rats and humans: application of a substrate depletion assay using hepatocytes for assessment of nonlinearity. Drug Metab Dispos 33:726–732.
  • Konig, F., Wolfersdorf, M., Loble, M., Wossner, S. Hauger, B. (1997). Trimipramine and maprotiline plasma levels during combined treatment with moclobemide in therapy-resistant depression. Pharmacopsychiatry 30:125–127.
  • Koren, G., Cairns, J., Chitayat, D., Gaedigk, A. Leeder, S. J. (2006). Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet 368:704.
  • Kosaki, K., Tamura, K., Sato, R., Samejima, H., Tanigawara, Y. Takahashi, T. (2004). A major influence of CYP2C19 genotype on the steady-state concentration of N-desmethylclobazam. Brain Dev 26:530–534.
  • Koskela, S., Hakkola, J., Hukkanen, J., Pelkonen, O., Sorri, M., Saranen, A., Anttila, S., Fernandez-Salguero, P., Gonzalez, F. Raunio, H. (1999). Expression of CYP2A genes in human liver and extrahepatic tissues. Biochem Pharmacol 57:1407–1413.
  • Kostrubsky, V. E., Sinclair, J. F., Ramachandran, V., Venkataramanan, R., Wen, Y. H., Kindt, E., Galchev, V., Rose, K., Sinz, M. Strom, S. C. (2000). The role of conjugation in hepatotoxicity of troglitazone in human and porcine hepatocyte cultures. Drug Metab Dispos 28:1192–1197.
  • Kotekar, A. Bhisey, R. (2000). CYP1A1*2 and CYP1A1*3 polymorphisms cosegregate in the Indian population. Anthropol Anz 60:255–260.
  • Koue, T., Kubo, M., Funaki, T., Fukuda, T., Azuma, J., Takaai, M., Kayano, Y. Hashimoto, Y. (2007). Nonlinear mixed effects model analysis of the pharmacokinetics of aripiprazole in healthy Japanese males. Biol Pharm Bull 30:2154–2158.
  • Kouri, R. E., McKinney, C. E., Slomiany, D. J., Snodgrass, D. R., Wray, N. P. McLemore, T. L. (1982). Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res 42:5030–5037.
  • Koyama, E., Chiba, K., Tani, M. Ishizaki, T. (1996). Identification of human cytochrome P450 isoforms involved in the stereoselective metabolism of mianserin enantiomers. J Pharmacol Exp Ther 278:21–30.
  • Koyama, E., Chiba, K., Tani, M. Ishizaki, T. (1997a). Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther 281:1199–1210.
  • Koyama, E., Chiba, K., Tani, M. Ishizaki, T. (1997b). Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther 281:1199–1210.
  • Kramer, M. A., Rettie, A. E., Rieder, M. J., Cabacungan, E. T. Hines, R. N. (2008). Novel CYP2C9 promoter variants and assessment of their impact on gene expression. Mol Pharmacol 73:1751–1760.
  • Kraus, D. M., Fischer, J. H., Reitz, S. J., Kecskes, S. A., Yeh, T. F., McCulloch, K. M., Tung, E. C. Cwik, M. J. (1993). Alterations in theophylline metabolism during the first year of life. Clin Pharmacol Ther 54:351–359.
  • Kreth, K., Kovar, K., Schwab, M. Zanger, U. M. (2000). Identification of the human cytochromes P450 involved in the oxidative metabolism of “Ecstasy”-related designer drugs. Biochem Pharmacol 59:1563–1571.
  • Krieter, P. A., Colletti, A. E., Doss, G. A. Miller, R. R. (1994). Disposition and metabolism of the hypoglycemic agent pioglitazone in rats. Drug Metab Dispos 22:625–630.
  • Kris, M. G., Hesketh, P. J., Somerfield, M. R., Feyer, P., Clark-Snow, R., Koeller, J. M., Morrow, G. R., Chinnery, L. W., Chesney, M. J., Gralla, R. J. Grunberg, S. M. (2006). American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24:2932–2947.
  • Kristensen, K., Christensen, C. B. Christrup, L. L. (1995). The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine. Life Sci 56:PL45–PL50.
  • Kristensen, V. N. Borresen-Dale, A. L. (2000). Molecular epidemiology of breast cancer: genetic variation in steroid hormone metabolism. Mutat Res 462:323–333.
  • Kroemer, H. K., Fischer, C., Meese, C. O. Eichelbaum, M. (1991). Enantiomer/enantiomer interaction of (S)- and (R)- propafenone for cytochrome P450IID6-catalyzed 5-hydroxylation: in vitro evaluation of the mechanism. Mol Pharmacol 40:135–142.
  • Kroemer, H. K., Fromm, M. F., Buhl, K., Terefe, H., Blaschke, G. Eichelbaum, M. (1994). An enantiomer-enantiomer interaction of (S)- and (R)-propafenone modifies the effect of racemic drug therapy. Circulation 89:2396–2400.
  • Kroemer, H. K., Funck-Brentano, C., Silberstein, D. J., Wood, A. J., Eichelbaum, M., Woosley, R. L. Roden, D. M. (1989a). Stereoselective disposition and pharmacologic activity of propafenone enantiomers. Circulation 79:1068–1076.
  • Kroemer, H. K., Gautier, J. C., Beaune, P., Henderson, C., Wolf, C. R. Eichelbaum, M. (1993). Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn Schmiedebergs Arch Pharmacol 348:332–337.
  • Kroemer, H. K., Mikus, G., Kronbach, T., Meyer, U. A. Eichelbaum, M. (1989b). In vitro characterization of the human cytochrome P-450 involved in polymorphic oxidation of propafenone. Clin Pharmacol Ther 45:28–33.
  • Kubo, M., Koue, T., Inaba, A., Takeda, H., Maune, H., Fukuda, T. Azuma, J. (2005). Influence of itraconazole co-administration and CYP2D6 genotype on the pharmacokinetics of the new antipsychotic ARIPIPRAZOLE. Drug Metab Pharmacokinet 20:55–64.
  • Kubo, M., Koue, T., Maune, H., Fukuda, T. Azuma, J. (2007). Pharmacokinetics of aripiprazole, a new antipsychotic, following oral dosing in healthy adult Japanese volunteers: influence of CYP2D6 polymorphism. Drug Metab Pharmacokinet 22:358–366.
  • Kubota, T., Nakajima-Taniguchi, C., Fukuda, T., Funamoto, M., Maeda, M., Tange, E., Ueki, R., Kawashima, K., Hara, H., Fujio, Y. Azuma, J. (2006). CYP2A6 polymorphisms are associated with nicotine dependence and influence withdrawal symptoms in smoking cessation. Pharmacogenomics J 6:115–119.
  • Kubota, T., Yamaura, Y., Ohkawa, N., Hara, H. Chiba, K. (2000). Frequencies of CYP2D6 mutant alleles in a normal Japanese population and metabolic activity of dextromethorphan O-demethylation in different CYP2D6 genotypes. Br J Clin Pharmacol 50:31–34.
  • Kudo, S. Ishizaki, T. (1999). Pharmacokinetics of haloperidol: an update. Clin Pharmacokinet 37:435–456.
  • Kudo, S. Odomi, M. (1998). Involvement of human cytochrome P450 3A4 in reduced haloperidol oxidation. Eur J Clin Pharmacol 54:253–259.
  • Kudo, S., Okumura, H., Miyamoto, G. Ishizaki, T. (1999). Cytochrome P-450 isoforms involved in carboxylic acid ester cleavage of Hantzsch pyridine ester of pranidipine. Drug Metab Dispos 27:303–308.
  • Kuehl, G. E., Lampe, J. W., Potter, J. D. Bigler, J. (2005). Glucuronidation of nonsteroidal anti-inflammatory drugs: identifying the enzymes responsible in human liver microsomes. Drug Metab Dispos 33:1027–1035.
  • Kuehl, G. E. Murphy, S. E. (2003). N-glucuronidation of nicotine and cotinine by human liver microsomes and heterologously expressed UDP-glucuronosyltransferases. Drug Metab Dispos 31:1361–1368.
  • Kuehl, P., Zhang, J., Lin, Y., Lamba, J., Assem, M., Schuetz, J., Watkins, P. B., Daly, A., Wrighton, S. A., Hall, S. D., Maurel, P., Relling, M., Brimer, C., Yasuda, K., Venkataramanan, R., Strom, S., Thummel, K., Boguski, M. S. Schuetz, E. (2001). Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 27:383–391.
  • Kumar, S., Samuel, K., Subramanian, R., Braun, M. P., Stearns, R. A., Chiu, S. H., Evans, D. C. Baillie, T. A. (2002). Extrapolation of diclofenac clearance from in vitro microsomal metabolism data: role of acyl glucuronidation and sequential oxidative metabolism of the acyl glucuronide. J Pharmacol Exp Ther 303:969–978.
  • Kumar, V., Wahlstrom, J. L., Rock, D. A., Warren, C. J., Gorman, L. A. Tracy, T. S. (2006). CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab Dispos 34:1966–1975.
  • Kuper, J. I. D’Aprile, M. (2000). Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet 39:203–214.
  • Kupfer, A. Branch, R. A. (1985). Stereoselective mephobarbital hydroxylation cosegregates with mephenytoin hydroxylation. Clin Pharmacol Ther 38:414–418.
  • Kusumoto, M., Ueno, K., Oda, A., Takeda, K., Mashimo, K., Takaya, K., Fujimura, Y., Nishihori, T. Tanaka, K. (2001). Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men. Clin Pharmacol Ther 69:104–107.
  • Kusumoto, M., Ueno, K., Tanaka, K., Takeda, K., Mashimo, K., Kameda, T., Fujimura, Y. Shibakawa, M. (1998). Lack of pharmacokinetic interaction between mexiletine and omeprazole. Ann Pharmacother 32:182–184.
  • Kutz, K. (1993). Pharmacology, toxicology and human pharmacokinetics of tropisetron. Ann Oncol 4(Suppl 3):15–18.
  • Labbe, L., Abolfathi, Z., Lessard, E., Pakdel, H., Beaune, P. Turgeon, J. (2003). Role of specific cytochrome P450 enzymes in the N-oxidation of the antiarrhythmic agent mexiletine. Xenobiotica 33:13–25.
  • Labbe, L., O’Hara, G., Lefebvre, M., Lessard, E., Gilbert, M., Adedoyin, A., Champagne, J., Hamelin, B. Turgeon, J. (2000). Pharmacokinetic and pharmacodynamic interaction between mexiletine and propafenone in human beings. Clin Pharmacol Ther 68:44–57.
  • Labbe, L., Robitaille, N. M., Lefez, C., Potvin, D., Gilbert, M., O’Hara, G. Turgeon, J. (2004). Effects of ciprofloxacin on the stereoselective disposition of mexiletine in man. Ther Drug Monit 26:492–498.
  • Labbe, L. Turgeon, J. (1999). Clinical pharmacokinetics of mexiletine. Clin Pharmacokinet 37:361–384.
  • Lacomblez, L., Bensimon, G., Leigh, P. N., Guillet, P. Meininger, V. (1996a). Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis/Riluzole Study Group II. Lancet 347:1425–1431.
  • Lacomblez, L., Bensimon, G., Leigh, P. N., Guillet, P., Powe, L., Durrleman, S., Delumeau, J. C. Meininger, V. (1996b). A confirmatory dose-ranging study of riluzole in ALS. ALS/Riluzole Study Group-II. Neurology 47:S242–S250.
  • Lai, J., Vesprini, D., Chu, W., Jernstrom, H. Narod, S. A. (2001). CYP gene polymorphisms and early menarche. Mol Genet Metab 74:449–457.
  • Lai, M. L., Wang, S. L., Lai, M. D., Lin, E. T., Tse, M. Huang, J. D. (1995). Propranolol disposition in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther 58:264–268.
  • Laizure, S. C., DeVane, C. L., Stewart, J. T., Dommisse, C. S. Lai, A. A. (1985). Pharmacokinetics of bupropion and its major basic metabolites in normal subjects after a single dose. Clin Pharmacol Ther 38:586–589.
  • Lake, B. G., Gaudin, H., Price, R. J. Walters, D. G. (1992). Metabolism of [3-14C]coumarin to polar and covalently bound products by hepatic microsomes from the rat, Syrian hamster, gerbil, and humans. Food Chem Toxicol 30:105–115.
  • Lal, S., Jada, S. R., Xiang, X., Lim, W. T., Lee, E. J. Chowbay, B. (2006). Pharmacogenetics of target genes across the warfarin pharmacological pathway. Clin Pharmacokinet 45:1189–1200.
  • Lam, Y. W., Gaedigk, A., Ereshefsky, L., Alfaro, C. L. Simpson, J. (2002). CYP2D6 inhibition by selective serotonin reuptake inhibitors: analysis of achievable steady-state plasma concentrations and the effect of ultrarapid metabolism at CYP2D6. Pharmacotherapy 22:1001–1006.
  • Lamba, J. K., Lin, Y. S., Thummel, K., Daly, A., Watkins, P. B., Strom, S., Zhang, J. Schuetz, E. G. (2002). Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics 12:121–132.
  • Lamba, V., Lamba, J., Yasuda, K., Strom, S., Davila, J., Hancock, M. L., Fackenthal, J. D., Rogan, P. K., Ring, B., Wrighton, S. A. Schuetz, E. G. (2003). Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression. J Pharmacol Exp Ther 307:906–922.
  • Lambrecht, R. W., Sinclair, P. R., Gorman, N. Sinclair, J. F. (1992). Uroporphyrinogen oxidation catalyzed by reconstituted cytochrome P450IA2. Arch Biochem Biophys 294:504–510.
  • Lambrecht, R. W., Thapar, M. Bonkovsky, H. L. (2007). Genetic aspects of porphyria cutanea tarda. Semin Liver Dis 27:99–108.
  • Landi, M. T., Bertazzi, P. A., Shields, P. G., Clark, G., Lucier, G. W., Garte, S. J., Cosma, G. Caporaso, N. E. (1994). Association between CYP1A1 genotype, mRNA expression, and enzymatic activity in humans. Pharmacogenetics 4:242–246.
  • Lane, H. Y., Hu, O. Y., Jann, M. W., Deng, H. C., Lin, H. N. Chang, W. H. (1997). Dextromethorphan phenotyping and haloperidol disposition in schizophrenic patients. Psychiatry Res 69:105–111.
  • Lang, T., Hitzl, M., Burk, O., Mornhinweg, E., Keil, A., Kerb, R., Klein, K., Zanger, U. M., Eichelbaum, M. Fromm, M. F. (2004a). Genetic polymorphisms in the multidrug resistance–associated protein 3 (ABCC3, MRP3) gene and relationship to its mRNA and protein expression in human liver. Pharmacogenetics 14:155–164.
  • Lang, T., Klein, K., Fischer, J., Nussler, A. K., Neuhaus, P., Hofmann, U., Eichelbaum, M., Schwab, M. Zanger, U. M. (2001). Extensive genetic polymorphism in the human CYP2B6 gene with impact on expression and function in human liver. Pharmacogenetics 11:399–415.
  • Lang, T., Klein, K., Richter, T., Zibat, A., Kerb, R., Eichelbaum, M., Schwab, M. Zanger, U. M. (2004b). Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: demonstration of phenotypic null alleles. J Pharmacol Exp Ther 311:34–43.
  • Langan-Fahey, S. M., Tormey, D. C. Jordan, V. C. (1990). Tamoxifen metabolites in patients on long-term adjuvant therapy for breast cancer. Eur J Cancer 26:883–888.
  • Langer, O. (2007). Oral antihyperglycemic agents for the management of gestational diabetes mellitus. Obstet Gynecol Clin North Am 34:255–274, ix.
  • Larsen, J. T. Brosen, K. (2005). Consumption of charcoal-broiled meat as an experimental tool for discerning CYP1A2-mediated drug metabolism in vivo. Basic Clin Pharmacol Toxicol 97:141–148.
  • Lasker, J. M., Chen, W. B., Wolf, I., Bloswick, B. P., Wilson, P. D. Powell, P. K. (2000). Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney. Role of Cyp4F2 and Cyp4A11. J Biol Chem 275:4118–4126.
  • Lasker, J. M., Wester, M. R., Aramsombatdee, E. Raucy, J. L. (1998). Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Arch Biochem Biophys 353:16–28.
  • Le Gal, A., Dreano, Y., Lucas, D., Berthou, F. (2003). Diversity of selective environmental substrates for human cytochrome P450 2A6: alkoxyethers, nicotine, coumarin, N-nitrosodiethylamine, and N-nitrosobenzylmethylamine. Toxicol Lett 144:77–91.
  • Le Liboux, A., Cachia, J. P., Kirkesseli, S., Gautier, J. Y., Guimart, C., Montay, G., Peeters, P. A., Groen, E., Jonkman, J. H. Wemer, J. (1999). A comparison of the pharmacokinetics and tolerability of riluzole after repeat dose administration in healthy elderly and young volunteers. J Clin Pharmacol 39:480–486.
  • Le Liboux, A., Lefebvre, P., Le Roux, Y., Truffinet, P., Aubeneau, M., Kirkesseli, S., Montay, G. (1997). Single- and multiple-dose pharmacokinetics of riluzole in white subjects. J Clin Pharmacol 37:820–827.
  • Le Marchand, L., Donlon, T., Kolonel, L. N., Henderson, B. E. Wilkens, L. R. (2005). Estrogen metabolism-related genes and breast cancer risk: the multiethnic cohort study. Cancer Epidemiol Biomarkers Prev 14:1998–2003.
  • Leathart, J. B., London, S. J., Steward, A., Adams, J. D., Idle, J. R. Daly, A. K. (1998). CYP2D6 phenotype-genotype relationships in African-Americans and Caucasians in Los Angeles. Pharmacogenetics 8:529–541.
  • Lee, A. J., Cai, M. X., Thomas, P. E., Conney, A. H. Zhu, B. T. (2003a). Characterization of the oxidative metabolites of 17beta- estradiol and estrone formed by 15 selectively expressed human cytochrome p450 isoforms. Endocrinology 144:3382–3398.
  • Lee, A. J., Kosh, J. W., Conney, A. H. Zhu, B. T. (2001). Characterization of the NADPH-dependent metabolism of 17beta-estradiol to multiple metabolites by human liver microsomes and selectively expressed human cytochrome P450 3A4 and 3A5. J Pharmacol Exp Ther 298:420–432.
  • Lee, A. M., Jepson, C., Hoffmann, E., Epstein, L., Hawk, L. W., Lerman, C. Tyndale, R. F. (2007a). CYP2B6 genotype alters abstinence rates in a bupropion smoking cessation trial. Biol Psychiatry 62:635–641.
  • Lee, A. Y., Kim, M. J., Chey, W. Y., Choi, J. Kim, B. G. (2004). Genetic polymorphism of cytochrome P450 2C9 in diphenylhydantoin-induced cutaneous adverse drug reactions. Eur J Clin Pharmacol 60:155–159.
  • Lee, C. R., Pieper, J. A., Frye, R. F., Hinderliter, A. L., Blaisdell, J. A. Goldstein, J. A. (2003b). Differences in flurbiprofen pharmacokinetics between CYP2C9*1/*1, *1/*2, and *1/*3 genotypes. Eur J Clin Pharmacol 58:791–794.
  • Lee, C. R., Pieper, J. A., Frye, R. F., Hinderliter, A. L., Blaisdell, J. A. Goldstein, J. A. (2003c). Tolbutamide, flurbiprofen, and losartan as probes of CYP2C9 activity in humans. J Clin Pharmacol 43:84–91.
  • Lee, C. R., Pieper, J. A., Hinderliter, A. L., Blaisdell, J. A. Goldstein, J. A. (2003d). Losartan and E3174 pharmacokinetics in cytochrome P450 2C9*1/*1, *1/*2, and *1/*3 individuals. Pharmacotherapy 23:720–725.
  • Lee, C. R., Plosker, G. L. McTavish, D. (1993). Tropisetron. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential as an antiemetic. Drugs 46:925–943.
  • Lee, E. J., Zhao, B., Moochhala, S. M. Ngoi, S. S. (1994). Frequency of mutant CYP1A1, NAT2, and GSTM1 alleles in a normal Chinese population. Pharmacogenetics 4:355–358.
  • Lee, J. T., Kroemer, H. K., Silberstein, D. J., Funck-Brentano, C., Lineberry, M. D., Wood, A. J., Roden, D. M. Woosley, R. L. (1990). The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med 322:1764–1768.
  • Lee, S. J., Usmani, K. A., Chanas, B., Ghanayem, B., Xi, T., Hodgson, E., Mohrenweiser, H. W. Goldstein, J. A. (2003e). Genetic findings and functional studies of human CYP3A5 single-nucleotide polymorphisms in different ethnic groups. Pharmacogenetics 13:461–472.
  • Lee, S. J., van der Heiden, I. P., Goldstein, J. A. van Schaik, R. H. (2007b). A new CYP3A5 variant, CYP3A5*11, is shown to be defective in nifedipine metabolism in a recombinant cDNA expression system. Drug Metab Dispos 35:67–71.
  • Lehmann, J. M., Moore, L. B., Smith-Oliver, T. A., Wilkison, W. O., Willson, T. M. Kliewer, S. A. (1995). An antidiabetic thiazolidinedione is a high-affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 270:12953–12956.
  • Lehnerer, M., Schulze, J., Achterhold, K., Lewis, D. F. Hlavica, P. (2000). Identification of key residues in rabbit liver microsomal cytochrome P450 2B4: importance in interactions with NADPH-cytochrome P450 reductase. J Biochem 127:163–169.
  • Lekas, P., Tin, K. L., Lee, C. Prokipcak, R. D. (2000). The human cytochrome P450 1A1 mRNA is rapidly degraded in HepG2 cells. Arch Biochem Biophys 384:311–318.
  • Lemoine, A., Gautier, J. C., Azoulay, D., Kiffel, L., Belloc, C., Guengerich, F. P., Maurel, P., Beaune, P. Leroux, J. P. (1993). Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol Pharmacol 43:827–832.
  • Lemoine, P., Nir, T., Laudon, M. Zisapel, N. (2007). Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res 16:372–380.
  • Lennard, M. S., Silas, J. H., Freestone, S. Trevethick, J. (1982). Defective metabolism of metoprolol in poor hydroxylators of debrisoquine. Br J Clin Pharmacol 14:301–303.
  • Lennard, M. S., Tucker, G. T., Silas, J. H., Freestone, S., Ramsay, L. E. Woods, H. F. (1983). Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers. Clin Pharmacol Ther 34:732–737.
  • Leo, M. A., Lasker, J. M., Raucy, J. L., Kim, C. I., Black, M. Lieber, C. S. (1989). Metabolism of retinol and retinoic acid by human liver cytochrome P450IIC8. Arch Biochem Biophys 269:305–312.
  • Leon, J., Susce, M. T., Pan, R. M., Wedlund, P. J., Orrego, M. L. Diaz, F. J. (2007). A study of genetic (CYP2D6 and ABCB1) and environmental (drug inhibitors and inducers) variables that may influence plasma risperidone levels. Pharmacopsychiatry 40:93–102.
  • Lerman, C., Shields, P. G., Wileyto, E. P., Audrain, J., Pinto, A., Hawk, L., Krishnan, S., Niaura, R. Epstein, L. (2002). Pharmacogenetic investigation of smoking cessation treatment. Pharmacogenetics 12:627–634.
  • Lesesve, J. F., Callat, M. P., Lenormand, B., Monconduit, M., Noblet, C., Moore, N., Caron, F., Humbert, G., Stamatoullas, A. Tilly, H. (1994). Hematological toxicity of ticlopidine. Am J Hematol 47:149–150.
  • Lessard, E., Fortin, A., Belanger, P. M., Beaune, P., Hamelin, B. A. Turgeon, J. (1997). Role of CYP2D6 in the N-hydroxylation of procainamide. Pharmacogenetics 7:381–390.
  • Lessard, E., Yessine, M. A., Hamelin, B. A., Gauvin, C., Labbe, L., O’Hara, G., LeBlanc, J. Turgeon, J. (2001). Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. J Clin Psychopharmacol 21:175–184.
  • Lessard, E., Yessine, M. A., Hamelin, B. A., O’Hara, G., LeBlanc, J. Turgeon, J. (1999). Influence of CYP2D6 activity on the disposition and cardiovascular toxicity of the antidepressant agent venlafaxine in humans. Pharmacogenetics 9:435–443.
  • Levin, M. D., den Hollander, J. G., van der Holt, B., Rijnders, B. J., van Vliet, M., Sonneveld, P., van Schaik, R. H. (2007). Hepatotoxicity of oral and intravenous voriconazole in relation to cytochrome P450 polymorphisms. J Antimicrob Chemother 60:1104–1107.
  • Li, D., Jiao, L., Li, Y., Doll, M. A., Hein, D. W., Bondy, M. L., Evans, D. B., Wolff, R. A., Lenzi, R., Pisters, P. W., Abbruzzese, J. L. Hassan, M. M. (2006a). Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer. Carcinogenesis 27:103–111.
  • Li, G., Gong, P. L., Qiu, J., Zeng, F. D. Klotz, U. (1998). Stereoselective steady state disposition and action of propafenone in Chinese subjects. Br J Clin Pharmacol 46:441–445.
  • Li, H. Poulos, T. L. (1997). The structure of the cytochrome p450BM-3 haem domain complexed with the fatty acid substrate, palmitoleic acid. Nat Struct Biol 4:140–146.
  • Li, L., Pan, R. M., Porter, T. D., Jensen, N. S., Silber, P., Russo, G., Tine, J. A., Heim, J., Ring, B. Wedlund, P. J. (2006b). New cytochrome P450 2D6*56 allele identified by genotype/phenotype analysis of cryopreserved human hepatocytes. Drug Metab Dispos 34:1411–1416.
  • Li, X. F., Carter, S., Dovichi, N. J., Zhao, J. Y., Kovarik, P. Sakuma, T. (2001). Analysis of tamoxifen and its metabolites in synthetic gastric fluid digests and urine samples using high-performance liquid chromatography with electrospray mass spectrometry. J Chromatogr A 914:5–12.
  • Li, X. Q., Bjorkman, A., Andersson, T. B., Ridderstrom, M. Masimirembwa, C. M. (2002). Amodiaquine clearance and its metabolism to N-desethylamodiaquine is mediated by CYP2C8: a new high affinity and turnover enzyme-specific probe substrate. J Pharmacol Exp Ther 300:399–407.
  • Li, X. Q., Weidolf, L., Simonsson, R. Andersson, T. B. (2005). Enantiomer/enantiomer interactions between the S- and R- isomers of omeprazole in human cytochrome P450 enzymes: major role of CYP2C19 and CYP3A4. J Pharmacol Exp Ther 315:777–787.
  • Li, Y., Li, N. Y. Sellers, E. M. (1997). Comparison of CYP2A6 catalytic activity on coumarin 7-hydroxylation in human and monkey liver microsomes. Eur J Drug Metab Pharmacokinet 22:295–304.
  • Libersa, C., Caron, J., Broly, F., Lacroix, D. Lhermitte, M. (1993). Interaction of propafenone and mexiletine. J Am Coll Cardiol 22:2061–2062.
  • Lien, E. A., Solheim, E., Lea, O. A., Lundgren, S., Kvinnsland, S. Ueland, P. M. (1989). Distribution of 4-hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in human biological fluids during tamoxifen treatment. Cancer Res 49:2175–2183.
  • Lim, C. K., Yuan, Z. X., Lamb, J. H., White, I. N., De Matteis, F., Smith, L. L. (1994). A comparative study of tamoxifen metabolism in female rat, mouse and human liver microsomes. Carcinogenesis 15:589–593.
  • Lim, H. S., Ju Lee, H., Seok Lee, K., Sook Lee, E., Jang, I. J. Ro, J. (2007). Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. J Clin Oncol 25:3837–3845.
  • Lin, C. J., Yang, J. C., Uang, Y. S., Chern, H. D. Wang, T. H. (2003). Time-dependent amplified pharmacokinetic and pharmacodynamic responses of rabeprazole in cytochrome P450 2C19 poor metabolizers. Pharmacotherapy 23:711–719.
  • Lin, G., Hawes, E. M., McKay, G., Korchinski, E. D. Midha, K. K. (1993). Metabolism of piperidine-type phenothiazine antipsychotic agents. IV. Thioridazine in dog, man and rat. Xenobiotica 23:1059–1074.
  • Lin, J. H. Lu, A. Y. (2001). Interindividual variability in inhibition and induction of cytochrome P450 enzymes. Annu Rev Pharmacol Toxicol 41:535–567.
  • Lin, K. M. Finder, E. (1983). Am. J. Psychiatry 140:490–495.
  • Lin, L. Y., Di Stefano, E. W., Schmitz, D. A., Hsu, L., Ellis, S. W., Lennard, M. S., Tucker, G. T. Cho, A. K. (1997). Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos 25:1059–1064.
  • Lindh, J. D., Annas, A., Meurling, L., Dahl, M. L. A, A. L.,-S. (2003). Effect of ketoconazole on venlafaxine plasma concentrations in extensive and poor metabolisers of debrisoquine. Eur J Clin Pharmacol 59:401–406.
  • Linnet, K. Olesen, O. V. (1997). Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes. Drug Metab Dispos 25:1379–1382.
  • Linnet, K. Wiborg, O. (1996). Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. Clin Pharmacol Ther 60:41–47.
  • Lintz, W., Erlacin, S., Frankus, E. Uragg, H. (1981). [Biotransformation of tramadol in man and animal (author’s transl)]. Arzneimittelforschung 31:1932–1943.
  • Liu, C., Zhuo, X., Gonzalez, F. J. Ding, X. (1996). Baculovirus-mediated expression and characterization of rat CYP2A3 and human CYP2a6: role in metabolic activation of nasal toxicants. Mol Pharmacol 50:781–788.
  • Liu, Y. L., Zhang, W., Tan, Z. R., Ouyang, D. S., Luo, C. H., Liu, Z. Q., Qiu, Y., Chen, Y., He, Y. J., Zhou, G. Zhou, H. H. (2006). Effect of the CYP2C9*3 allele on lornoxicam metabolism. Clin Chim Acta 364:287–291.
  • Liu, Z. C. Uetrecht, J. P. (2000). Metabolism of ticlopidine by activated neutrophils: implications for ticlopidine-induced agranulocytosis. Drug Metab Dispos 28:726–730.
  • Liu, Z. Q., Cheng, Z. N., Huang, S. L., Chen, X. P., Ou-Yang, D. S., Jiang, C. H. Zhou, H. H. (2001). Effect of the CYP2C19 oxidation polymorphism on fluoxetine metabolism in Chinese healthy subjects. Br J Clin Pharmacol 52:96–99.
  • Liu, Z. Q., Zhu, B., Tan, Y. F., Tan, Z. R., Wang, L. S., Huang, S. L., Shu, Y. Zhou, H. H. (2002). O-dealkylation of fluoxetine in relation to CYP2C19 gene dose and involvement of CYP3A4 in human liver microsomes. J Pharmacol Exp Ther 300:105–111.
  • Llerena, A., Alm, C., Dahl, M. L., Ekqvist, B. Bertilsson, L. (1992a). Haloperidol disposition is dependent on debrisoquine hydroxylation phenotype. Ther Drug Monit 14:92–97.
  • Llerena, A., Berecz, R., de la Rubia A., Dorado, P. (2002). QTc interval lengthening is related to CYP2D6 hydroxylation capacity and plasma concentration of thioridazine in patients. J Psychopharmacol 16:361–364.
  • Llerena, A., Berecz, R., de la Rubia, A., Norberto, M. J. Benitez, J. (2000). Use of the mesoridazine/thioridazine ratio as a marker for CYP2D6 enzyme activity. Ther Drug Monit 22:397–401.
  • Llerena, A., Dahl, M. L., Ekqvist, B. Bertilsson, L. (1992b). Haloperidol disposition is dependent on the debrisoquine hydroxylation phenotype: increased plasma levels of the reduced metabolite in poor metabolizers. Ther Drug Monit 14:261–264.
  • Llerena, A., Dorado, P. Penas-Lledo, E. M. (2009). Pharmacogenetics of debrisoquine and its use as a marker for CYP2D6 hydroxylation capacity. Pharmacogenomics 10:17–28.
  • Lo, M. W., Goldberg, M. R., McCrea, J. B., Lu, H., Furtek, C. I. Bjornsson, T. D. (1995). Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans. Clin Pharmacol Ther 58:641–649.
  • Loboz, K. K., Gross, A. S., Williams, K. M., Liauw, W. S., Day, R. O., Blievernicht, J. K., Zanger, U. M. McLachlan, A. J. (2006). Cytochrome P450 2B6 activity as measured by bupropion hydroxylation: effect of induction by rifampin and ethnicity. Clin Pharmacol Ther 80:75–84.
  • Locniskar, A. Greenblatt, D. J. (1990). Oxidative versus conjugative biotransformation of temazepam. Biopharm Drug Dispos 11:499–506.
  • Lofgren, S., Baldwin, R. M., Hiratsuka, M., Lindqvist, A., Carlberg, A., Sim, S. C., Schulke, M., Snait, M., Edenro, A., Fransson-Steen, R., Terelius, Y. Ingelman-Sundberg, M. (2008). Generation of mice transgenic for human CYP2C18 and CYP2C19: characterization of the sexually dimorphic gene and enzyme expression. Drug Metab Dispos 36:955–962.
  • Loi, C. M., Young, M., Randinitis, E., Vassos, A. Koup, J. R. (1999). Clinical pharmacokinetics of troglitazone. Clin Pharmacokinet 37:91–104.
  • London, S. J., Yuan, J. M., Coetzee, G. A., Gao, Y. T., Ross, R. K. Yu, M. C. (2000). CYP1A1 I462V genetic polymorphism and lung cancer risk in a cohort of men in Shanghai, China. Cancer Epidemiol Biomarkers Prev 9:987–991.
  • Longley, D. B., Harkin, D. P. Johnston, P. G. (2003). 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer 3:330–338.
  • Lopez-Garcia, M. P., Dansette, P. M. Mansuy, D. (1994). Thiophene derivatives as new mechanism-based inhibitors of cytochromes P-450: inactivation of yeast-expressed human liver cytochrome P-450 2C9 by tienilic acid. Biochemistry 33:66–175.
  • Loriot, M. A., Rebuissou, S., Oscarson, M., Cenee, S., Miyamoto, M., Ariyoshi, N., Kamataki, T., Hemon, D., Beaune, P. Stucker, I. (2001). Genetic polymorphisms of cytochrome P450 2A6 in a case-control study on lung cancer in a French population. Pharmacogenetics 11:39–44.
  • Lotsch, J., Skarke, C., Liefhold, J. Geisslinger, G. (2004). Genetic predictors of the clinical response to opioid analgesics: clinical utility and future perspectives. Clin Pharmacokinet 43:983–1013.
  • Lovlie, R., Daly, A. K., Idle, J. R. Steen, V. M. (1997). Characterization of the 16 + 9 kb and 30 + 9 kb CYP2D6 XbaI haplotypes. Pharmacogenetics 7:149–152.
  • Loy, C. Schneider, L. (2006). Galantamine for Alzheimer’s disease and mild cognitive impairment. Cochrane Database Syst Rev CD001747.
  • Ludeman, S. M. (1999). The chemistry of the metabolites of cyclophosphamide. Curr Pharm Des 5:627–643.
  • Lundblad, M. S., Ohlsson, S., Johansson, P., Lafolie, P. Eliasson, E. (2006). Accumulation of celecoxib with a 7-fold higher drug exposure in individuals homozygous for CYP2C9*3. Clin Pharmacol Ther 79:287–288.
  • Lundblad, M. S., Stark, K., Eliasson, E., Oliw, E. Rane, A. (2005). Biosynthesis of epoxyeicosatrienoic acids varies between polymorphic CYP2C enzymes. Biochem Biophys Res Commun 327:1052–1057.
  • Luo, H., Hawes, E. M., McKay, G., Korchinski, E. D. Midha, K. K. (1991). N(+)-glucuronidation of aliphatic tertiary amines, a general phenomenon in the metabolism of H1-antihistamines in humans. Xenobiotica 21:1281–1288.
  • Lurie, G., Maskarinec, G., Kaaks, R., Stanczyk, F. Z. Le Marchand, L. (2005). Association of genetic polymorphisms with serum estrogens measured multiple times during a 2-year period in premenopausal women. Cancer Epidemiol Biomarkers Prev 14:1521–1527.
  • Lutz, M., Schwab, M., Griese, E. U., Marx, C., Muller-Oerlinghausen, B., Schonhofer, P. S., Meisner, C., Gleiter, C. H., Eichelbaum, M. Morike, K. (2002). Visual disorders associated with omeprazole and their relation to CYP2C19 polymorphism. Pharmacogenetics 12:73–75.
  • Ma, X., Idle, J. R., Krausz, K. W. Gonzalez, F. J. (2005). Metabolism of melatonin by human cytochromes p450. Drug Metab Dispos 33:489–494.
  • Machinist, J. M., Mayer, M. D., Shet, M. S., Ferrero, J. L. Rodrigues, A. D. (1995). Identification of the human liver cytochrome P450 enzymes involved in the metabolism of zileuton (ABT-077) and its N-dehydroxylated metabolite, Abbott-66193. Drug Metab Dispos 23:1163–1174.
  • Madadi, P., Ross, C. J., Hayden, M. R., Carleton, B. C., Gaedigk, A., Leeder, J. S. Koren, G. (2009). Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clin Pharmacol Ther 85:31–35.
  • Madan, A., Parkinson, A. Faiman, M. D. (1998). Identification of the human P-450 enzymes responsible for the sulfoxidation and thiono-oxidation of diethyldithiocarbamate methyl ester: role of P-450 enzymes in disulfiram bioactivation. Alcohol Clin Exp Res 22:1212–1219.
  • Madani, S., Paine, M. F., Lewis, L., Thummel, K. E. Shen, D. D. (1999). Comparison of CYP2D6 content and metoprolol oxidation between microsomes isolated from human livers and small intestines. Pharm Res 16:1199–1205.
  • Maekawa, K., Fukushima-Uesaka, H., Tohkin, M., Hasegawa, R., Kajio, H., Kuzuya, N., Yasuda, K., Kawamoto, M., Kamatani, N., Suzuki, K., Yanagawa, T., Saito, Y. Sawada, J. (2006). Four novel defective alleles and comprehensive haplotype analysis of CYP2C9 in Japanese. Pharmacogenet Genomics 16:497–514.
  • Maes, M., Westenberg, H., Vandoolaeghe, E., Demedts, P., Wauters, A., Neels, H. Meltzer, H. Y. (1997). Effects of trazodone and fluoxetine in the treatment of major depression: therapeutic pharmacokinetic and pharmacodynamic interactions through formation of meta-chlorophenylpiperazine. J Clin Psychopharmacol 17:358–364.
  • Maeshiba, Y., Kiyota, Y., Yamashita, K., Yoshimura, Y., Motohashi, M. Tanayama, S. (1997). Disposition of the new antidiabetic agent pioglitazone in rats, dogs, and monkeys. Arzneimittelforschung 47:29–35.
  • Maguire, J. H. (1988). Quantitative estimation of catechol/methylcatechol pathways in human phenytoin metabolism. Epilepsia 29:753–759.
  • Mahgoub, A., Idle, J. R., Dring, L. G., Lancaster, R. Smith, R. L. (1977). Polymorphic hydroxylation of Debrisoquine in man. Lancet 2:584–586.
  • Malfatto, G., Zaza, A., Forster, M., Sodowick, B., Danilo, P., Jr, Rosen, M. R. (1988). Electrophysiologic, inotropic and antiarrhythmic effects of propafenone, 5-hydroxypropafenone and N-depropylpropafenone. J Pharmacol Exp Ther 246: 419–426.
  • Malinowski, J. M. Bolesta, S. (2000). Rosiglitazone in the treatment of type 2 diabetes mellitus: a critical review. Clin Ther 22:1151–1168; discussion, 1149-1150.
  • Mamiya, K., Hadama, A., Yukawa, E., Ieiri, I., Otsubo, K., Ninomiya, H., Tashiro, N. Higuchi, S. (2000). CYP2C19 polymorphism effect on phenobarbitone. Pharmacokinetics in Japanese patients with epilepsy: analysis by population pharmacokinetics. Eur J Clin Pharmacol 55:821–825.
  • Mamiya, K., Ieiri, I., Shimamoto, J., Yukawa, E., Imai, J., Ninomiya, H., Yamada, H., Otsubo, K., Higuchi, S. Tashiro, N. (1998). The effects of genetic polymorphisms of CYP2C9 and CYP2C19 on phenytoin metabolism in Japanese adult patients with epilepsy: studies in stereoselective hydroxylation and population pharmacokinetics. Epilepsia 39:1317–1323.
  • Mani, C., Gelboin, H. V., Park, S. S., Pearce, R., Parkinson, A. Kupfer, D. (1993a). Metabolism of the antimammary cancer antiestrogenic agent tamoxifen. I. Cytochrome P-450-catalyzed N-demethylation and 4-hydroxylation. Drug Metab Dispos 21:645–656.
  • Mani, C., Hodgson, E. Kupfer, D. (1993b). Metabolism of the antimammary cancer antiestrogenic agent tamoxifen. II. Flavin-containing monooxygenase-mediated N-oxidation. Drug Metab Dispos 21:657–661.
  • Mankowski, D. C. (1999). The role of CYP2C19 in the metabolism of (+/-) bufuralol, the prototypic substrate of CYP2D6. Drug Metab Dispos 27:1024–1028.
  • Mannens, G. S., Snel, C. A., Hendrickx, J., Verhaeghe, T., Le Jeune, L., Bode, W., van Beijsterveldt, L., Lavrijsen, K., Leempoels, J., Van Osselaer, N., Van Peer, A., Meuldermans, W. (2002). The metabolism and excretion of galantamine in rats, dogs, and humans. Drug Metab Dispos 30:553–563.
  • Mano, Y., Usui, T. Kamimura, H. (2007). Predominant contribution of UDP-glucuronosyltransferase 2B7 in the glucuronidation of racemic flurbiprofen in the human liver. Drug Metab Dispos 35:1182–1187.
  • Manolis, A. S., Deering, T. F., Cameron, J. Estes, N. A.3rd. (1990). Mexiletine: pharmacology and therapeutic use. Clin Cardiol 13:349–359.
  • Maraganore, D. M., Farrer, M. J., Hardy, J. A., McDonnell, S. K., Schaid, D. J. Rocca, W. A. (2000). Case-control study of debrisoquine 4-hydroxylase, N-acetyltransferase 2, and apolipoprotein E gene polymorphisms in Parkinson’s disease. Mov Disord 15:714–719.
  • Marez-Allorge, D., Ellis, S. W., Lo Guidice, J. M., Tucker, G. T. Broly, F. (1999). A rare G2061 insertion affecting the open reading frame of CYP2D6 and responsible for the poor metabolizer phenotype. Pharmacogenetics 9:393–396.
  • Marez, D., Legrand, M., Sabbagh, N., Guidice, J. M., Spire, C., Lafitte, J. J., Meyer, U. A. Broly, F. (1997). Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics 7:193–202.
  • Marez, D., Legrand, M., Sabbagh, N., Lo-Guidice, J. M., Boone, P. Broly, F. (1996). An additional allelic variant of the CYP2D6 gene causing impaired metabolism of sparteine. Hum Genet 97:668–670.
  • Marez, D., Sabbagh, N., Legrand, M., Lo-Guidice, J. M., Boone, P. Broly, F. (1995). A novel CYP2D6 allele with an abolished splice recognition site associated with the poor metabolizer phenotype. Pharmacogenetics 5:305–311.
  • Margolis, J. M., O’Donnell, J. P., Mankowski, D. C., Ekins, S. Obach, R. S. (2000). (R)-, (S)-, and racemic fluoxetine N-demethylation by human cytochrome P450 enzymes. Drug Metab Dispos 28:1187–1191.
  • Marill, J., Capron, C. C., Idres, N. Chabot, G. G. (2002). Human cytochrome P450s involved in the metabolism of 9-cis- and 13-cis-retinoic acids. Biochem Pharmacol 63:933–943.
  • Marill, J., Cresteil, T., Lanotte, M. Chabot, G. G. (2000). Identification of human cytochrome P450s involved in the formation of all- trans-retinoic acid principal metabolites. Mol Pharmacol 58: 1341–1348.
  • Marino, M. R., Langenbacher, K., Ford, N. F. Uderman, H. D. (1998). Pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects. J Clin Pharmacol 38:246–255.
  • Marino, M. R. Vachharajani, N. N. (2002). Pharmacokinetics of irbesartan are not altered in special populations. J Cardiovasc Pharmacol 40:112–122.
  • Marone, G., Plaut, M. Lichtenstein, L. M. (1978). Characterization of a specific adenosine receptor on human lymphocytes. J Immunol 121:2153–2159.
  • Marsh, S., Somlo, G., Li, X., Frankel, P., King, C. R., Shannon, W. D., McLeod, H. L. Synold, T. W. (2007). Pharmacogenetic analysis of paclitaxel transport and metabolism genes in breast cancer. Pharmacogenomics J 7:362–365.
  • Martin, J. H., Begg, E. J., Kennedy, M. A., Roberts, R. Barclay, M. L. (2001). Is cytochrome P450 2C9 genotype associated with NSAID gastric ulceration? Br J Clin Pharmacol 51:627–630.
  • Martinez-Selles, M., Castillo, I., Montenegro, P., Martin, M. L., Almendral, J. Sanjurjo, M. (2005). [Pharmacogenetic study of the response to flecainide and propafenone in patients with atrial fibrillation]. Rev Esp Cardiol 58:745–748.
  • Martinez, C., Blanco, G., Ladero, J. M., Garcia-Martin, E., Taxonera, C., Gamito, F. G., Diaz-Rubio, M. Agundez, J. A. (2004). Genetic predisposition to acute gastrointestinal bleeding after NSAIDs use. Br J Pharmacol 141:205–208.
  • Martinez, C., Garcia-Martin, E., Blanco, G., Gamito, F. J., Ladero, J. M. Agundez, J. A. (2005). The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)-ibuprofen enantiomer in healthy subjects. Br J Clin Pharmacol 59:62–69.
  • Martinez Perez-Balsa, A., De Arce, A., Castiella, A., Lopez, P., Ruibal, M., Ruiz-Martinez, J., Lopez De Munain, A., Marti Masso, J. F. (1998). Hepatotoxicity due to ticlopidine. Ann Pharmacother 32:1250–1251.
  • Marzolini, C., Telenti, A., Decosterd, L. A., Greub, G., Biollaz, J. Buclin, T. (2001). Efavirenz plasma levels can predict treatment failure and central nervous system side effects in HIV-1-infected patients. Aids 15:71–75.
  • Masimirembwa, C., Persson, I., Bertilsson, L., Hasler, J. Ingelman-Sundberg, M. (1996). A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity. Br J Clin Pharmacol 42:713–719.
  • Masubuchi, Y., Hosokawa, S., Horie, T., Suzuki, T., Ohmori, S., Kitada, M. Narimatsu, S. (1994). Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-desisopropylase. Drug Metab Dispos 22:909–915.
  • Masubuchi, Y., Iwasa, T., Hosokawa, S., Suzuki, T., Horie, T., Imaoka, S., Funae, Y. Narimatsu, S. (1997). Selective deficiency of debrisoquine 4-hydroxylase activity in mouse liver microsomes. J Pharmacol Exp Ther 282:1435–1441.
  • Masubuchi, Y., Umeda, S., Chiba, M., Fujita, S. Suzuki, T. (1991). Selective 3-hydroxylation deficiency of lidocaine and its metabolite in Dark Agouti rats. Biochem Pharmacol 42:693–695.
  • Matheson, A. J. Jarvis, B. (2001). Lansoprazole: an update of its place in the management of acid-related disorders. Drugs 61:1801–1833.
  • Matimba, A., Del-Favero, J., Van Broeckhoven C., Masimirembwa, C. (2009). Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects. Hum Genomics 3:169–190.
  • Matsui, K., Mishima, M., Nagai, Y., Yuzuriha, T. Yoshimura, T. (1999a). Absorption, distribution, metabolism, and excretion of donepezil (Aricept) after a single oral administration to Rat. Drug Metab Dispos 27:1406–1414.
  • Matsui, K., Taniguchi, S. Yoshimura, T. (1999b). Correlation of the intrinsic clearance of donepezil (Aricept) between in vivo and in vitro studies in rat, dog, and human. Xenobiotica 29:1059–1072.
  • Matsumoto, S. Yamazoe, Y. (2001). Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine. Br J Clin Pharmacol 51:133–142.
  • Matsunaga, E., Zanger, U. M., Hardwick, J. P., Gelboin, H. V., Meyer, U. A. Gonzalez, F. J. (1989). The CYP2D gene subfamily: analysis of the molecular basis of the debrisoquine 4-hydroxylase deficiency in DA rats. Biochemistry 28:7349–7355.
  • Matsunaga, M., Yamazaki, H., Kiyotani, K., Iwano, S., Saruwatari, J., Nakagawa, K., Soyama, A., Ozawa, S., Sawada, J. I., Kashiyama, E., Kinoshita, M. Kamataki, T. (2009). Two novel CYP2D6*10 haplotypes as possible causes of a poor metabolic phenotype in Japanese. Drug Metab Dispos 37:699–701.
  • Mattila, M. A. Larni, H. M. (1980). Flunitrazepam: a review of its pharmacological properties and therapeutic use. Drugs 20:353–374.
  • Maurer, H. H. (1990). Identification of antiarrhythmic drugs and their metabolites in urine. Arch Toxicol 64:218–230.
  • Mautz, D. S., Nelson, W. L. Shen, D. D. (1995). Regioselective and stereoselective oxidation of metoprolol and bufuralol catalyzed by microsomes containing cDNA-expressed human P4502D6. Drug Metab Dispos 23:513–517.
  • McAllister, C. B., Wolfenden, H. T., Aslanian, W. S., Woosley, R. L. Wilkinson, G. R. (1986). Oxidative metabolism of encainide: polymorphism, pharmacokinetics, and clinical considerations. Xenobiotica 16:483–490.
  • McAlpine, D. E., O’Kane, D. J., Black, J. L. Mrazek, D. A. (2007). Cytochrome P450 2D6 genotype variation and venlafaxine dosage. Mayo Clin Proc 82:1065–1068.
  • McCague, R., Parr, I. B. Haynes, B. P. (1990). Metabolism of the 4-iodo derivative of tamoxifen by isolated rat hepatocytes. Demonstration that the iodine atom reduces metabolic conversion and identification of four metabolites. Biochem Pharmacol 40:2277–2283.
  • McCague, R. Seago, A. (1986). Aspects of metabolism of tamoxifen by rat liver microsomes. Identification of a new metabolite: E-1-[4-(2-dimethylaminoethoxy)-phenyl]-1, 2-diphenyl-1-buten-3-ol N-oxide. Biochem Pharmacol 35:827–834.
  • McGeer, P. L., Boulding, J. E., Gibson, W. C. Foulkes, R. G. (1961). Drug-induced extrapyramidal reactions. Treatment with diphenhydramine hydrochloride and dihydroxyphenylalanine. JAMA 177: 665–670.
  • McGourty, J. C., Silas, J. H., Lennard, M. S., Tucker, G. T. Woods, H. F. (1985). Metoprolol metabolism and debrisoquine oxidation polymorphism–population and family studies. Br J Clin Pharmacol 20:555–566.
  • McKeage, K. Perry, C. M. (2003). Propofol: a review of its use in intensive care sedation of adults. CNS Drugs 17:235–272.
  • McKinnon, R. A., Burgess, W. M., Hall, P. M., Roberts-Thomson, S. J., Gonzalez, F. J. McManus, M. E. (1995). Characterisation of CYP3A gene subfamily expression in human gastrointestinal tissues. Gut 36:259–267.
  • McLaughlin, L. A., Paine, M. J., Kemp, C. A., Marechal, J. D., Flanagan, J. U., Ward, C. J., Sutcliffe, M. J., Roberts, G. C. Wolf, C. R. (2005). Why is quinidine an inhibitor of cytochrome P450 2D6? The role of key active-site residues in quinidine binding. J Biol Chem 280:38617–38624.
  • McLellan, R. A., Oscarson, M., Seidegard, J., Evans, D. A. Ingelman-Sundberg, M. (1997). Frequent occurrence of CYP2D6 gene duplication in Saudi Arabians. Pharmacogenetics 7:187–191.
  • McLemore, T. L., Martin, R. R., Springer, R. R., Wray, N., Cantrell, E. T. Busbee, D. L. (1979). Aryl hydrocarbon hydroxylase activity in pulmonary alveolar macrophages and lymphocytes from lung cancer and noncancer patients: a correlation with family histories of cancer. Biochem Genet 17:795–806.
  • McLeod, H. L. (2001). Pharmacogenetics: more than skin deep. Nat Genet 29:247–248.
  • McLeod, H. L. Evans, W. E. (2001). Pharmacogenomics: unlocking the human genome for better drug therapy. Annu Rev Pharmacol Toxicol 41:101–121.
  • McQuinn, R. L., Pentikainen, P. J., Chang, S. F. Conard, G. J. (1988). Pharmacokinetics of flecainide in patients with cirrhosis of the liver. Clin Pharmacol Ther 44:566–572.
  • McQuinn, R. L., Quarfoth, G. J., Johnson, J. D., Banitt, E. H., Pathre, S. V., Chang, S. F., Ober, R. E. Conard, G. J. (1984). Biotransformation and elimination of 14C-flecainide acetate in humans. Drug Metab Dispos 12:414–420.
  • McSorley, L. C. Daly, A. K. (2000). Identification of human cytochrome P450 isoforms that contribute to all-trans-retinoic acid 4-hydroxylation. Biochem Pharmacol 60:517–526.
  • Meadowcroft, A. M., Williamson, K. M., Patterson, J. H., Hinderliter, A. L. Pieper, J. A. (1999). The effects of fluvastatin, a CYP2C9 inhibitor, on losartan pharmacokinetics in healthy volunteers. J Clin Pharmacol 39:418–424.
  • Mehvar, R., Brocks, D. R. Vakily, M. (2002). Impact of stereoselectivity on the pharmacokinetics and pharmacodynamics of antiarrhythmic drugs. Clin Pharmacokinet 41:533–558.
  • Melkersson, K. I., Scordo, M. G., Gunes, A. Dahl, M. L. (2007). Impact of CYP1A2 and CYP2D6 polymorphisms on drug metabolism and on insulin and lipid elevations and insulin resistance in clozapine-treated patients. J Clin Psychiatry 68:697–704.
  • Mellstrom, B., Bertilsson, L., Sawe, J., Schulz, H. U. Sjoqvist, F. (1981). E- and Z-10-hydroxylation of nortriptyline: relationship to polymorphic debrisoquine hydroxylation. Clin Pharmacol Ther 30:189–193.
  • Mellstrom, B., Sawe, J., Bertilsson, L. Sjoqvist, F. (1986). Amitriptyline metabolism: association with debrisoquin hydroxylation in nonsmokers. Clin Pharmacol Ther 39:369–371.
  • Mellstrom, B. von Bahr C. (1981). Demethylation and hydroxylation of amitriptyline, nortriptyline, and 10-hydroxyamitriptyline in human liver microsomes. Drug Metab Dispos 9:565–568.
  • Melzacka, M., Boksa, J. Maj, J. (1979). 1-(m-chlorophenyl)piperazine: a metabolite of trazodone isolated from rat urine. J Pharm Pharmacol 31:855–856.
  • Mendez, M., Sorkin, L., Rossetti, M. V., Astrin, K. H., del, C. B. A. M., Parera, V. E., Aizencang, G. Desnick, R. J. (1998). Familial porphyria cutanea tarda: characterization of seven novel uroporphyrinogen decarboxylase mutations and frequency of common hemochromatosis alleles. Am J Hum Genet 63:1363–1375.
  • Messina, E. S., Tyndale, R. F. Sellers, E. M. (1997). A major role for CYP2A6 in nicotine C-oxidation by human liver microsomes. J Pharmacol Exp Ther 282:1608–1614.
  • Mihara, K., Kondo, T., Suzuki, A., Yasui-Furukori, N., Ono, S., Otani, K. Kaneko, S. (2001). Effects of genetic polymorphism of CYP1A2 inducibility on the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine in depressed Japanese patients. Pharmacol Toxicol 88:267–270.
  • Mihara, K., Otani, K., Suzuki, A., Yasui, N., Nakano, H., Meng, X., Ohkubo, T., Nagasaki, T., Kaneko, S., Tsuchida, S., Sugawara, K. Gonzalez, F. J. (1997a). Relationship between the CYP2D6 genotype and the steady-state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine. Psychopharmacology (Berl) 133:95–98.
  • Mihara, K., Otani, K., Tybring, G., Dahl, M. L., Bertilsson, L. Kaneko, S. (1997b). The CYP2D6 genotype and plasma concentrations of mianserin enantiomers in relation to therapeutic response to mianserin in depressed Japanese patients. J Clin Psychopharmacol 17:467–471.
  • Mihara, K., Suzuki, A., Kondo, T., Yasui, N., Furukori, H., Nagashima, U., Otani, K., Kaneko, S. Inoue, Y. (1999). Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia. Clin Pharmacol Ther 65:291–294.
  • Mikhailova, O. N., Gulyaeva, L. F., Prudnikov, A. V., Gerasimov, A. V. Krasilnikov, S. E. (2006). Estrogen-metabolizing gene polymorphisms in the assessment of female hormone-dependent cancer risk. Pharmacogenomics J 6:189–193.
  • Miksys, S., Rao, Y., Hoffmann, E., Mash, D. C. Tyndale, R. F. (2002). Regional and cellular expression of CYP2D6 in human brain: higher levels in alcoholics. J Neurochem 82:1376–1387.
  • Miksys, S., Rao, Y., Sellers, E. M., Kwan, M., Mendis, D. Tyndale, R. F. (2000). Regional and cellular distribution of CYP2D subfamily members in rat brain. Xenobiotica 30:547–564.
  • Miksys, S. L., Cheung, C., Gonzalez, F. J. Tyndale, R. F. (2005). Human CYP2D6 and mouse CYP2Ds: organ distribution in a humanized mouse model. Drug Metab Dispos 33:1495–1502.
  • Mikus, G., Bochner, F., Eichelbaum, M., Horak, P., Somogyi, A. A. Spector, S. (1994). Endogenous codeine and morphine in poor and extensive metabolisers of the CYP2D6 (debrisoquine/sparteine) polymorphism. J Pharmacol Exp Ther 268:546–551.
  • Mikus, G., Gross, A. S., Beckmann, J., Hertrampf, R., Gundert-Remy, U. Eichelbaum, M. (1989). The influence of the sparteine/debrisoquin phenotype on the disposition of flecainide. Clin Pharmacol Ther 45:562–567.
  • Mikus, G., Morike, K., Griese, E. U. Klotz, U. (1998). Relevance of deficient CYP2D6 in opiate dependence. Pharmacogenetics 8:565–568.
  • Mikus, G., Schowel, V., Drzewinska, M., Rengelshausen, J., Ding, R., Riedel, K. D., Burhenne, J., Weiss, J., Thomsen, T. Haefeli, W. E. (2006). Potent cytochrome P450 2C19 genotype-related interaction between voriconazole and the cytochrome P450 3A4 inhibitor ritonavir. Clin Pharmacol Ther 80:126–135.
  • Milano, G., Etienne, M. C., Frenay, M., Khater, R., Formento, J. L., Renee, N., Moll, J. L., Francoual, M., Berto, M. Namer, M. (1987). Optimised analysis of tamoxifen and its main metabolites in the plasma and cytosol of mammary tumours. Br J Cancer 55:509–512.
  • Mildvan, D., Yarrish, R., Marshak, A., Hutman, H. W., McDonough, M., Lamson, M. Robinson, P. (2002). Pharmacokinetic interaction between nevirapine and ethinyl estradiol/norethindrone when administered concurrently to HIV-infected women. J Acquir Immune Defic Syndr 29:471–477.
  • Miles, J. S., Bickmore, W., Brook, J. D., McLaren, A. W., Meehan, R. Wolf, C. R. (1989). Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity. Nucleic Acids Res 17:2907–2917.
  • Miles, J. S., McLaren, A. W., Forrester, L. M., Glancey, M. J., Lang, M. A. Wolf, C. R. (1990). Identification of the human liver cytochrome P-450 responsible for coumarin 7-hydroxylase activity. Biochem J 267:365–371.
  • Milinkovic, A. Martinez, E. (2004). Nevirapine in the treatment of HIV. Expert Rev Anti Infect Ther 2:367–373.
  • Miller, M., Opheim, K. E., Raisys, V. A. Motulsky, A. G. (1984). Theophylline metabolism: variation and genetics. Clin Pharmacol Ther 35:170–182.
  • Miller, R. G., Mitchell, J. D., Lyon, M. Moore, D. H. (2007). Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev CD001447.
  • Min, D. I. Ellingrod, V. L. (2003). Association of the CYP3A4*1B 5’-flanking region polymorphism with cyclosporine pharmacokinetics in healthy subjects. Ther Drug Monit 25:305–309.
  • Minder, E. I., Meier, P. J., Muller, H. K., Minder, C. Meyer, U. A. (1984). Bufuralol metabolism in human liver: a sensitive probe for the debrisoquine-type polymorphism of drug oxidation. Eur J Clin Invest 14:184–189.
  • Miners, J. O. Birkett, D. J. (1998). Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 45:525–538.
  • Miners, J. O., Coulter, S., Tukey, R. H., Veronese, M. E. Birkett, D. J. (1996). Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. Biochem Pharmacol 51:1003–1008.
  • Miners, J. O., Rees, D. L., Valente, L., Veronese, M. E. Birkett, D. J. (1995). Human hepatic cytochrome P450 2C9 catalyzes the rate-limiting pathway of torsemide metabolism. J Pharmacol Exp Ther 272:1076–1081.
  • Mitsunaga, Y., Kubota, T., Ishiguro, A., Yamada, Y., Sasaki, H., Chiba, K. Iga, T. (2002). Frequent occurrence of CYP2D6*10 duplication allele in a Japanese population. Mutat Res 505:83–85.
  • Mittal, R. D. Srivastava, D. L. (2007). Cytochrome P4501A1 and microsomal epoxide hydrolase gene polymorphisms: gene-environment interaction and risk of prostate cancer. DNA Cell Biol 26:791–798.
  • Miura, M., Kagaya, H., Tada, H., Uno, T., Yasui-Furukori, N., Tateishi, T. Suzuki, T. (2006a). Enantioselective disposition of rabeprazole in relation to CYP2C19 genotypes. Br J Clin Pharmacol 61:315–320.
  • Miura, M. Ohkubo, T. (2004). In vitro metabolism of quazepam in human liver and intestine and assessment of drug interactions. Xenobiotica 34:1001–1011.
  • Miura, M., Otani, K. Ohkubo, T. (2005). Identification of human cytochrome P450 enzymes involved in the formation of 4-hydroxyestazolam from estazolam. Xenobiotica 35:455–465.
  • Miura, M., Satoh, S., Tada, H., Habuchi, T. Suzuki, T. (2006b). Stereoselective metabolism of rabeprazole-thioether to rabeprazole by human liver microsomes. Eur J Clin Pharmacol 62:113–117.
  • Miyamoto, M., Umetsu, Y., Dosaka-Akita, H., Sawamura, Y., Yokota, J., Kunitoh, H., Nemoto, N., Sato, K., Ariyoshi, N. Kamataki, T. (1999). CYP2A6 gene deletion reduces susceptibility to lung cancer. Biochem Biophys Res Commun 261:658–660.
  • Miyoshi, M., Mizuno, M., Ishiki, K., Nagahara, Y., Maga, T., Torigoe, T., Nasu, J., Okada, H., Yokota, K., Oguma, K. Tsuji, T. (2001). A randomized, open trial for comparison of proton pump inhibitors, omeprazole versus rabeprazole, in dual therapy for Helicobacter pylori infection in relation to CYP2C19 genetic polymorphism. J Gastroenterol Hepatol 16:723–728.
  • Mizuno, C. S., Chittiboyina, A. G., Kurtz, T. W., Pershadsingh, H. A. Avery, M. A. (2008). Type 2 diabetes and oral antihyperglycemic drugs. Curr Med Chem 15:61–74.
  • Mizutani, T. (2003). PM frequencies of major CYPs in Asians and Caucasians. Drug Metab Rev 35:99–106.
  • Modi, S., Gilham, D. E., Sutcliffe, M. J., Lian, L. Y., Primrose, W. U., Wolf, C. R. Roberts, G. C. (1997). 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase. Biochemistry 36:4461–4470.
  • Modi, S., Paine, M. J., Sutcliffe, M. J., Lian, L. Y., Primrose, W. U., Wolf, C. R. Roberts, G. C. (1996). A model for human cytochrome P450 2D6 based on homology modeling and NMR studies of substrate binding. Biochemistry 35:4540–4550.
  • Mooney, L. A., Bell, D. A., Santella, R. M., Van Bennekum, A. M., Ottman, R., Paik, M., Blaner, W. S., Lucier, G. W., Covey, L., Young, T. L., Cooper, T. B., Glassman, A. H. Perera, F. P. (1997). Contribution of genetic and nutritional factors to DNA damage in heavy smokers. Carcinogenesis 18:503–509.
  • Moore, L. B., Parks, D. J., Jones, S. A., Bledsoe, R. K., Consler, T. G., Stimmel, J. B., Goodwin, B., Liddle, C., Blanchard, S. G., Willson, T. M., Collins, J. L. Kliewer, S. A. (2000). Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J Biol Chem 275:15122–15127.
  • Moore, M. L. Zaccaro, D. J. (2000). Cigarette smoking, low birth weight, and preterm births in low-income African-American women. J Perinatol 20:176–180.
  • Moretti, A., Arcari, G. Pegrassi, L. (1979). [A review of pharmacological studies on nicergoline]. Arzneimittelforschung 29:1223–1227.
  • Mori, A., Maruo, Y., Iwai, M., Sato, H. Takeuchi, Y. (2005). UDP-glucuronosyltransferase 1A4 polymorphisms in a Japanese population and kinetics of clozapine glucuronidation. Drug Metab Dispos 33:672–675.
  • Morita, J., Kobayashi, K., Wanibuchi, A., Kimura, M., Irie, S., Ishizaki, T. Chiba, K. (2004). A novel single-nucleotide polymorphism (SNP) of the CYP2C19 gene in a Japanese subject with lowered capacity of mephobarbital 4’-hydroxylation. Drug Metab Pharmacokinet 19:236–238.
  • Morita, S., Shimoda, K., Someya, T., Yoshimura, Y., Kamijima, K. Kato, N. (2000). Steady-state plasma levels of nortriptyline and its hydroxylated metabolites in Japanese patients: impact of CYP2D6 genotype on the hydroxylation of nortriptyline. J Clin Psychopharmacol 20:141–149.
  • Morrison, H. G., Oleksiak, M. F., Cornell, N. W., Sogin, M. L. Stegeman, J. J. (1995). Identification of cytochrome P-450 1A (CYP1A) genes from two teleost fish, toadfish (Opsanus tau), and scup (Stenotomus chrysops), and phylogenetic analysis of CYP1A genes. Biochem J 308(Pt 1):97–104.
  • Mouly, S., Lown, K. S., Kornhauser, D., Joseph, J. L., Fiske, W. D., Benedek, I. H. Watkins, P. B. (2002). Hepatic, but not intestinal, CYP3A4 displays dose-dependent induction by efavirenz in humans. Clin Pharmacol Ther 72:1–9.
  • Moysich, K. B., Shields, P. G., Freudenheim, J. L., Schisterman, E. F., Vena, J. E., Kostyniak, P., Greizerstein, H., Marshall, J. R., Graham, S. Ambrosone, C. B. (1999). Polychlorinated biphenyls, cytochrome P4501A1 polymorphism, and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 8:41–44.
  • Mueller, R. A. Baur, H. R. (1986). Flecainide: a new antiarrhythmic drug. Clin Cardiol 9:1–5.
  • Murata, M., Shiraishi, T., Fukutome, K., Watanabe, M., Nagao, M., Kubota, Y., Ito, H., Kawamura, J. Yatani, R. (1998). Cytochrome P4501A1 and glutathione S-transferase M1 genotypes as risk factors for prostate cancer in Japan. Jpn J Clin Oncol 28:657–660.
  • Murayama, N., Imai, N., Nakane, T., Shimizu, M. Yamazaki, H. (2007). Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol 73:2020–2026.
  • Murayama, N., Nakamura, T., Saeki, M., Soyama, A., Saito, Y., Sai, K., Ishida, S., Nakajima, O., Itoda, M., Ohno, Y., Ozawa, S. Sawada, J. (2002). CYP3A4 gene polymorphisms influence testosterone 6beta-hydroxylation. Drug Metab Pharmacokinet 17:150–156.
  • Murayama, N., Soyama, A., Saito, Y., Nakajima, Y., Komamura, K., Ueno, K., Kamakura, S., Kitakaze, M., Kimura, H., Goto, Y., Saitoh, O., Katoh, M., Ohnuma, T., Kawai, M., Sugai, K., Ohtsuki, T., Suzuki, C., Minami, N., Ozawa, S. Sawada, J. (2004). Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes. J Pharmacol Exp Ther 308:300–306.
  • Murphy, C., Fotsis, T., Pantzar, P., Adlercreutz, H. Martin, F. (1987). Analysis of tamoxifen and its metabolites in human plasma by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). J Steroid Biochem 26:547–555.
  • Murphy, P. J. (1974). Metabolic pathways of aprindine. Acta Cardiol Suppl 18:131–142.
  • Murphy, R. L., Sommadossi, J. P., Lamson, M., Hall, D. B., Myers, M. Dusek, A. (1999). Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1. J Infect Dis 179:1116–1123.
  • Murphy, S. E., Johnson, L. M., Losey, L. M., Carmella, S. G. Hecht, S. S. (2001). Consumption of watercress fails to alter coumarin metabolism in humans. Drug Metab Dispos 29:786–788.
  • Murphy, S. E., Raulinaitis, V. Brown, K. M. (2005). Nicotine 5’-oxidation and methyl oxidation by P450 2A enzymes. Drug Metab Dispos 33:1166–1173.
  • Musial, A., Bajda, M. Malawska, B. (2007). Recent developments in cholinesterases inhibitors for Alzheimer’s disease treatment. Curr Med Chem 14:2654–2679.
  • Mutlib, A. E., Chen, H., Nemeth, G. A., Markwalder, J. A., Seitz, S. P., Gan, L. S. Christ, D. D. (1999). Identification and characterization of efavirenz metabolites by liquid chromatography/mass spectrometry and high-field NMR: species differences in the metabolism of efavirenz. Drug Metab Dispos 27:1319–1333.
  • Mwenifumbo, J. C., Al Koudsi, N., Ho, M. K., Zhou, Q., Hoffmann, E. B., Sellers, E. M. Tyndale, R. F. (2008a). Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent. Hum Mutat 29:679–688.
  • Mwenifumbo, J. C., Lessov-Schlaggar, C. N., Zhou, Q., Krasnow, R. E., Swan, G. E., Benowitz, N. L. Tyndale, R. F. (2008b). Identification of novel CYP2A6*1B variants: the CYP2A6*1B allele is associated with faster in vivo nicotine metabolism. Clin Pharmacol Ther 83:115–121.
  • Nadin, L. Murray, M. (1999). Participation of CYP2C8 in retinoic acid 4-hydroxylation in human hepatic microsomes. Biochem Pharmacol 58:1201–1208.
  • Nakachi, K., Imai, K., Hayashi, S. Kawajiri, K. (1993). Polymorphisms of the CYP1A1 and glutathione S-transferase genes associated with susceptibility to lung cancer in relation to cigarette dose in a Japanese population. Cancer Res 53:2994–2999.
  • Nakajima, M., Fujiki, Y., Kyo, S., Kanaya, T., Nakamura, M., Maida, Y., Tanaka, M., Inoue, M. Yokoi, T. (2005). Pharmacokinetics of paclitaxel in ovarian cancer patients and genetic polymorphisms of CYP2C8, CYP3A4, and MDR1. J Clin Pharmacol 45:674–682.
  • Nakajima, M., Fujiki, Y., Noda, K., Ohtsuka, H., Ohkuni, H., Kyo, S., Inoue, M., Kuroiwa, Y. Yokoi, T. (2003). Genetic polymorphisms of CYP2C8 in Japanese population. Drug Metab Dispos 31:687–690.
  • Nakajima, M., Fukami, T., Yamanaka, H., Higashi, E., Sakai, H., Yoshida, R., Kwon, J. T., McLeod, H. L. Yokoi, T. (2006a). Comprehensive evaluation of variability in nicotine metabolism and CYP2A6 polymorphic alleles in four ethnic populations. Clin Pharmacol Ther 80:282–297.
  • Nakajima, M., Itoh, M., Sakai, H., Fukami, T., Katoh, M., Yamazaki, H., Kadlubar, F. F., Imaoka, S., Funae, Y. Yokoi, T. (2006b). CYP2A13 expressed in human bladder metabolically activates 4-aminobiphenyl. Int J Cancer 119:2520–2526.
  • Nakajima, M., Itoh, M., Yamanaka, H., Fukami, T., Tokudome, S., Yamamoto, Y., Yamamoto, H. Yokoi, T. (2006c). Isoflavones inhibit nicotine C-oxidation catalyzed by human CYP2A6. J Clin Pharmacol 46:337–344.
  • Nakajima, M., Kobayashi, K., Shimada, N., Tokudome, S., Yamamoto, T. Kuroiwa, Y. (1998). Involvement of CYP1A2 in mexiletine metabolism. Br J Clin Pharmacol 46:55–62.
  • Nakajima, M., Komagata, S., Fujiki, Y., Kanada, Y., Ebi, H., Itoh, K., Mukai, H., Yokoi, T. Minami, H. (2007). Genetic polymorphisms of CYP2B6 affect the pharmacokinetics/pharmacodynamics of cyclophosphamide in Japanese cancer patients. Pharmacogenet Genomics 17:431–445.
  • Nakajima, M., Kwon, J. T., Tanaka, N., Zenta, T., Yamamoto, Y., Yamamoto, H., Yamazaki, H., Yamamoto, T., Kuroiwa, Y. Yokoi, T. (2001). Relationship between interindividual differences in nicotine metabolism and CYP2A6 genetic polymorphism in humans. Clin Pharmacol Ther 69:72–78.
  • Nakajima, M., Nakamura, S., Tokudome, S., Shimada, N., Yamazaki, H. Yokoi, T. (1999a). Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: evaluation of approach to predict the contribution of multiple CYPs. Drug Metab Dispos 27:1381–1391.
  • Nakajima, M., Yamamoto, T., Nunoya, K., Yokoi, T., Nagashima, K., Inoue, K., Funae, Y., Shimada, N., Kamataki, T. Kuroiwa, Y. (1996a). Characterization of CYP2A6 involved in 3’-hydroxylation of cotinine in human liver microsomes. J Pharmacol Exp Ther 277:1010–1015.
  • Nakajima, M., Yamamoto, T., Nunoya, K., Yokoi, T., Nagashima, K., Inoue, K., Funae, Y., Shimada, N., Kamataki, T. Kuroiwa, Y. (1996b). Role of human cytochrome P4502A6 in C-oxidation of nicotine. Drug Metab Dispos 24:1212–1217.
  • Nakajima, M. Yokoi, T. (2005). Interindividual variability in nicotine metabolism: C-oxidation and glucuronidation. Drug Metab Pharmacokinet 20:227–235.
  • Nakajima, M., Yokoi, T., Mizutani, M., Kinoshita, M., Funayama, M. Kamataki, T. (1999b). Genetic polymorphism in the 5’-flanking region of human CYP1A2 gene: effect on the CYP1A2 inducibility in humans. J Biochem 125:803–808.
  • Nakajima, M., Yokoi, T., Mizutani, M., Shin, S., Kadlubar, F. F. Kamataki, T. (1994). Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene. Cancer Epidemiol Biomarkers Prev 3:413–421.
  • Nakajima, M., Yoshida, R., Fukami, T., McLeod, H. L. Yokoi, T. (2004). Novel human CYP2A6 alleles confound gene deletion analysis. FEBS Lett 569:75–81.
  • Nakamura, K., Yokoi, T., Inoue, K., Shimada, N., Ohashi, N., Kume, T. Kamataki, T. (1996). CYP2D6 is the principal cytochrome P450 responsible for metabolism of the histamine H1 antagonist promethazine in human liver microsomes. Pharmacogenetics 6:449–457.
  • Nakamura, K., Yokoi, T., Kodama, T., Inoue, K., Nagashima, K., Shimada, N., Shimizu, T. Kamataki, T. (1998). Oxidation of histamine H1 antagonist mequitazine is catalyzed by cytochrome P450 2D6 in human liver microsomes. J Pharmacol Exp Ther 284:437–442.
  • Naoe, T., Takeyama, K., Yokozawa, T., Kiyoi, H., Seto, M., Uike, N., Ino, T., Utsunomiya, A., Maruta, A., Jin-nai, I., Kamada, N., Kubota, Y., Nakamura, H., Shimazaki, C., Horiike, S., Kodera, Y., Saito, H., Ueda, R., Wiemels, J. Ohno, R. (2000). Analysis of genetic polymorphism in NQO1, GST-M1, GST-T1, and CYP3A4 in 469 Japanese patients with therapy-related leukemia/ myelodysplastic syndrome and de novo acute myeloid leukemia. Clin Cancer Res 6:4091–4095.
  • Narimatsu, S., Tachibana, M., Masubuchi, Y. Suzuki, T. (1996). Cytochrome P4502D and -2C enzymes catalyze the oxidative N-demethylation of the Parkinsonism-inducing substance 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in rat liver microsomes. Chem Res Toxicol 9:93–98.
  • Narimatsu, S., Takemi, C., Tsuzuki, D., Kataoka, H., Yamamoto, S., Shimada, N., Suzuki, S., Satoh, T., Meyer, U. A. Gonzalez, F. J. (2002). Stereoselective metabolism of bufuralol racemate and enantiomers in human liver microsomes. J Pharmacol Exp Ther 303:172–178.
  • Naritomi, Y., Terashita, S. Kagayama, A. (2004). Identification and relative contributions of human cytochrome P450 isoforms involved in the metabolism of glibenclamide and lansoprazole: evaluation of an approach based on the in vitro substrate disappearance rate. Xenobiotica 34:415–427.
  • Nasu, K., Kubota, T. Ishizaki, T. (1997). Genetic analysis of CYP2C9 polymorphism in a Japanese population. Pharmacogenetics 7:405–409.
  • Nebert, D. W. Gonzalez, F. J. (1987). P450 genes: structure, evolution, and regulation. Annu Rev Biochem 56:945–993.
  • Nebert, D. W. Russell, D. W. (2002). Clinical importance of the cytochromes P450. Lancet 360:1155–1162.
  • Nelson, D. R., Zeldin, D. C., Hoffman, S. M., Maltais, L. J., Wain, H. M. Nebert, D. W. (2004). Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes, and alternative-splice variants. Pharmacogenetics 14:1–18.
  • Neugebauer, G., Akpan, W., Kaufmann, B. Reiff, K. (1990). Stereoselective disposition of carvedilol in man after intravenous and oral administration of the racemic compound. Eur J Clin Pharmacol 38(Suppl 2):S108–S111.
  • Neugebauer, G., Besenfelder, E. von Mollendorff, E. (1988). Pharmacokinetics and metabolism of torasemide in man. Arzneimittelforschung 38:164–166.
  • Newcomer, J. W. (2007). Antipsychotic medications: metabolic and cardiovascular risk. J Clin Psychiatry 68(Suppl 4):8–13.
  • Nicholl, D. J., Bennett, P., Hiller, L., Bonifati, V., Vanacore, N., Fabbrini, G., Marconi, R., Colosimo, C., Lamberti, P., Stocchi, F., Bonuccelli, U., Vieregge, P., Ramsden, D. B., Meco, G. Williams, A. C. (1999). A study of five candidate genes in Parkinson’s disease and related neurodegenerative disorders. European Study Group on Atypical Parkinsonism. Neurology 53:1415–1421.
  • Nielsen, K. K., Brosen, K. Gram, L. F. (1992). Steady-state plasma levels of clomipramine and its metabolites: impact of the sparteine/debrisoquine oxidation polymorphism. Danish University Antidepressant Group. Eur J Clin Pharmacol 43:405–411.
  • Nielsen, K. K., Brosen, K., Hansen, M. G. Gram, L. F. (1994). Single-dose kinetics of clomipramine: relationship to the sparteine and S-mephenytoin oxidation polymorphisms. Clin Pharmacol Ther 55:518–527.
  • Nielsen, K. K., Flinois, J. P., Beaune, P. Brosen, K. (1996). The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther 277:1659–1664.
  • Nielsen, T. L., Rasmussen, B. B., Flinois, J. P., Beaune, P. Brosen, K. (1999). In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes. J Pharmacol Exp Ther 289:31–37.
  • Niemi, M., Backman, J. T., Kajosaari, L. I., Leathart, J. B., Neuvonen M., Daly, A. K., Eichelbaum, M., Kivisto, K. T. Neuvonen, P. J. (2005). Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Clin Pharmacol Ther 77:468–478.
  • Niemi, M., Backman, J. T., Neuvonen, M. Neuvonen, P. J. (2003a). Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 46:347–351.
  • Niemi, M., Cascorbi, I., Timm, R., Kroemer, H. K., Neuvonen, P. J. Kivisto, K. T. (2002). Glyburide and glimepiride pharmacokinetics in subjects with different CYP2C9 genotypes. Clin Pharmacol Ther 72:326–332.
  • Niemi, M., Kajosaari, L. I., Neuvonen, M., Backman, J. T. Neuvonen, P. J. (2004). The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects. Br J Clin Pharmacol 57:441–447.
  • Niemi, M., Leathart, J. B., Neuvonen, M., Backman, J. T., Daly, A. K. Neuvonen, P. J. (2003b). Polymorphism in CYP2C8 is associated with reduced plasma concentrations of repaglinide. Clin Pharmacol Ther 74:380–387.
  • Niemi, M., Neuvonen, P. J. Kivisto, K. T. (2001). The cytochrome P4503A4 inhibitor clarithromycin increases the plasma concentrations and effects of repaglinide. Clin Pharmacol Ther 70:58–65.
  • Niitsu, Y., Jakubowski, J. A., Sugidachi, A. Asai, F. (2005). Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost 31:184–194.
  • Nishida, S. (2005). Metabolic effects of melatonin on oxidative stress and diabetes mellitus. Endocrine 27:131–136.
  • Nishimura, M., Yaguti, H., Yoshitsugu, H., Naito, S. Satoh, T. (2003). Tissue distribution of mRNA expression of human cytochrome P450 isoforms assessed by high-sensitivity real-time reverse transcription PCR. Yakugaku Zasshi 123:369–375.
  • Nitsch, J., Neyses, L., Kohler, U. Luderitz, B. (1987). [Elevated plasma flecainide concentrations in heart failure]. Dtsch Med Wochenschr 112:1698–1700.
  • Niwa, T., Sato, R., Yabusaki, Y., Ishibashi, F. Katagiri, M. (1999). Contribution of human hepatic cytochrome P450s and steroidogenic CYP17 to the N-demethylation of aminopyrine. Xenobiotica 29:187–193.
  • Niwa, T., Shiraga, T., Mitani, Y., Terakawa, M., Tokuma, Y. Kagayama, A. (2000). Stereoselective metabolism of cibenzoline, an antiarrhythmic drug, by human and rat liver microsomes: possible involvement of CYP2D and CYP3A. Drug Metab Dispos 28:1128–1134.
  • Noble, S. Goa, K. L. (1996). Ticlopidine. A review of its pharmacology, clinical efficacy and tolerability in the prevention of cerebral ischaemia and stroke. Drugs Aging 8:214–232.
  • Nomura, A., Sakurai, E. Hikichi, N. (1997). Stereoselective N-demethylation of chlorpheniramine by rat-liver microsomes and the involvement of cytochrome P450 isozymes. J Pharm Pharmacol 49:257–262.
  • Nordin, C. Bertilsson, L. (1995). Active hydroxymetabolites of antidepressants. Emphasis on E-10-hydroxy-nortriptyline. Clin Pharmacokinet 28:26–40.
  • Nordmark, A., Lundgren, S., Ask, B., Granath, F. Rane, A. (2002). The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women. Br J Clin Pharmacol 54:504–510.
  • Notarianni, L. J., Oliver, S. E., Dobrocky, P., Bennett, P. N. Silverman, B. W. (1995). Caffeine as a metabolic probe: a comparison of the metabolic ratios used to assess CYP1A2 activity. Br J Clin Pharmacol 39:65–69.
  • Nunoya, K., Yokoi, T., Kimura, K., Inoue, K., Kodama, T., Funayama, M., Nagashima, K., Funae, Y., Green, C., Kinoshita, M. Kamataki, T. (1998). A new deleted allele in the human cytochrome P450 2A6 (CYP2A6) gene found in individuals showing poor metabolic capacity to coumarin and (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502). Pharmacogenetics 8:239–249.
  • Nunoya, K., Yokoi, T., Takahashi, Y., Kimura, K., Kinoshita, M. Kamataki, T. (1999a). Homologous unequal cross-over within the human CYP2A gene cluster as a mechanism for the deletion of the entire CYP2A6 gene associated with the poor metabolizer phenotype. J Biochem 126:402–407.
  • Nunoya, K., Yokoi, Y., Kimura, K., Kodama, T., Funayama, M., Inoue, K., Nagashima, K., Funae, Y., Shimada, N., Green, C. Kamataki, T. (1996). (+)-cis-3,5-dimethyl-2-(3-pyridyl) thiazolidin-4-one hydrochloride (SM-12502) as a novel substrate for cytochrome P450 2A6 in human liver microsomes. J Pharmacol Exp Ther 277:768–774.
  • Nunoya, K. I., Yokoi, T., Kimura, K., Kainuma, T., Satoh, K., Kinoshita, M. Kamataki, T. (1999b). A new CYP2A6 gene deletion responsible for the in vivo polymorphic metabolism of (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride in humans. J Pharmacol Exp Ther 289:437–442.
  • Nyberg, S., Dahl, M. L. Halldin, C. (1995). A PET study of D2 and 5-HT2 receptor occupancy induced by risperidone in poor metabolizers of debrisoquin and risperidone. Psychopharmacology (Berl) 119:345–348.
  • O’Donnell, C. J., Grime, K., Courtney, P., Slee, D. Riley, R. J. (2007). The development of a cocktail CYP2B6, CYP2C8, and CYP3A5 inhibition assay and a preliminary assessment of utility in a drug discovery setting. Drug Metab Dispos 35:381–385.
  • O’Reilly, R. A. (1974). Studies on the optical enantiomorphs of warfarin in man. Clin Pharmacol Ther 16:348–354.
  • Obach, R. S. (2000). Metabolism of ezlopitant, a nonpeptidic substance P receptor antagonist, in liver microsomes: enzyme kinetics, cytochrome P450 isoform identity, and in vitro–in vivo correlation. Drug Metab Dispos 28:1069–1076.
  • Obach, R. S. (2001). Cytochrome P450-catalyzed metabolism of ezlopitant alkene (CJ-12,458), a pharmacologically active metabolite of ezlopitant: enzyme kinetics and mechanism of an alkene hydration reaction. Drug Metab Dispos 29:1057–1067.
  • Obach, R. S., Cox, L. M. Tremaine, L. M. (2005). Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study. Drug Metab Dispos 33:262–270.
  • Obase, Y., Shimoda, T., Kawano, T., Saeki, S., Tomari, S. Y., Mitsuta-Izaki, K., Matsuse, H., Kinoshita, M. Kohno, S. (2003). Polymorphisms in the CYP1A2 gene and theophylline metabolism in patients with asthma. Clin Pharmacol Ther 73:468–474.
  • Oda, Y., Aryal, P., Terashita, T., Gillam, E. M., Guengerich, F. P. Shimada, T. (2001a). Metabolic activation of heterocyclic amines and other procarcinogens in Salmonella typhimurium umu tester strains expressing human cytochrome P4501A1, 1A2, 1B1, 2C9, 2D6, 2E1, and 3A4 and human NADPH-P450 reductase and bacterial O-acetyltransferase. Mutat Res 492:81–90.
  • Oda, Y., Furuichi, K., Tanaka, K., Hiroi, T., Imaoka, S., Asada, A., Fujimori, M. Funae, Y. (1995). Metabolism of a new local anesthetic, ropivacaine, by human hepatic cytochrome P450. Anesthesiology 82:214–220.
  • Oda, Y., Hamaoka, N., Hiroi, T., Imaoka, S., Hase, I., Tanaka, K., Funae, Y., Ishizaki, T. Asada, A. (2001b). Involvement of human liver cytochrome P4502B6 in the metabolism of propofol. Br J Clin Pharmacol 51:281–285.
  • Oda, Y. Kharasch, E. D. (2001). Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation. J Pharmacol Exp Ther 298:1021–1032.
  • Odani, A., Hashimoto, Y., Otsuki, Y., Uwai, Y., Hattori, H., Furusho, K. Inui, K. (1997). Genetic polymorphism of the CYP2C subfamily and its effect on the pharmacokinetics of phenytoin in Japanese patients with epilepsy. Clin Pharmacol Ther 62:287–292.
  • Ogilvie, B. W., Zhang, D., Li, W., Rodrigues, A. D., Gipson, A. E., Holsapple, J., Toren, P. Parkinson, A. (2006). Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions. Drug Metab Dispos 34:191–197.
  • Ogura, K., Ishikawa, Y., Kaku, T., Nishiyama, T., Ohnuma, T., Muro, K. Hiratsuka, A. (2006). Quaternary ammonium-linked glucuronidation of trans-4-hydroxytamoxifen, an active metabolite of tamoxifen, by human liver microsomes and UDP-glucuronosyltransferase 1A4. Biochem Pharmacol 71:1358–1369.
  • Ohkusa, T., Maekawa, T., Arakawa, T., Nakajima, M., Fujimoto, K., Hoshino, E., Mitachi, Y., Hamada, S., Mine, T., Kawahara, Y., Nagai, T., Aoyama, N., Yoshida, N., Tadokoro, K., Chida, N., Konda, Y., Seno, H., Shimatani, T., Inoue, M. Sato, N. (2005). Effect of CYP2C19 polymorphism on the safety and efficacy of omeprazole in Japanese patients with recurrent reflux oesophagitis. Aliment Pharmacol Ther 21:1331–1339.
  • Ohno, S., Kawana, K. Nakajin, S. (2008). Contribution of UDP-glucuronosyltransferase 1A1 and 1A8 to morphine-6-glucuronidation and its kinetic properties. Drug Metab Dispos 36:688–694.
  • Ohnuma, T., Shibata, N., Matsubara, Y. Arai, H. (2003). Haloperidol plasma concentration in Japanese psychiatric subjects with gene duplication of CYP2D6. Br J Clin Pharmacol 56:315–320.
  • Ohta, S., Tachikawa, O., Makino, Y., Tasaki, Y. Hirobe, M. (1990). Metabolism and brain accumulation of tetrahydroisoquinoline (TIQ) a possible parkinsonism inducing substance, in an animal model of a poor debrisoquine metabolizer. Life Sci 46:599–605.
  • Ohyama, K., Nakajima, M., Nakamura, S., Shimada, N., Yamazaki, H. Yokoi, T. (2000). A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: an approach to predict the contribution with relative activity factor. Drug Metab Dispos 28:1303–1310.
  • Oldham, H. G. Clarke, S. E. (1997). In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R(+)- and S(-)-carvedilol. Drug Metab Dispos 25:970–977.
  • Olesen, O. V., Licht, R. W., Thomsen, E., Bruun, T., Viftrup, J. E. Linnet, K. (1998). Serum concentrations and side effects in psychiatric patients during risperidone therapy. Ther Drug Monit 20:380–384.
  • Olesen, O. V. Linnet, K. (1997). Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P-450 isozymes. Drug Metab Dispos 25:740–744.
  • Olesen, O. V. Linnet, K. (1999). Studies on the stereoselective metabolism of citalopram by human liver microsomes and cDNA- expressed cytochrome P450 enzymes. Pharmacology 59:298–309.
  • Olesen, O. V. Linnet, K. (2000). Identification of the human cytochrome P450 isoforms mediating in vitro N-dealkylation of perphenazine. Br J Clin Pharmacol 50:563–571.
  • Olesen, O. V. Linnet, K. (2001). Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations. J Clin Pharmacol 41:823–832.
  • Olsen, N. J. Stein, C. M. (2004). New drugs for rheumatoid arthritis. N Engl J Med 350:2167–2179.
  • Ono, S., Hatanaka, T., Miyazawa, S., Tsutsui, M., Aoyama, T., Gonzalez, F. J. Satoh, T. (1996). Human liver microsomal diazepam metabolism using cDNA-expressed cytochrome P450s: role of CYP2B6, 2C19, and the 3A subfamily. Xenobiotica 26:1155–1166.
  • Oosterhuis, M., Van De Kraats, G., Tenback, D. (2007). Safety of aripiprazole: high serum levels in a CYP2D6 mutated patient. Am J Psychiatry 164:175.
  • Orlando, R., Piccoli, P., De Martin, S., Padrini, R., Floreani, M., Palatini, P. (2004). Cytochrome P450 1A2 is a major determinant of lidocaine metabolism in vivo: effects of liver function. Clin Pharmacol Ther 75:80–88.
  • Osawa, Y., Osawa, K. K., Miyaishi, A., Higuchi, M., Tsutou, A., Matsumura, S., Tabuchi, Y., Tsubota, N. Takahashi, J. (2007). NAT2 and CYP1A2 polymorphisms and lung cancer risk in relation to smoking status. Asian Pac J Cancer Prev 8:103–108.
  • Osborne, C. K., Wiebe, V. J., McGuire, W. L., Ciocca, D. R. DeGregorio, M. W. (1992). Tamoxifen and the isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients. J Clin Oncol 10:304–310.
  • Osborne, M. R., Hewer, A., Hardcastle, I. R., Carmichael, P. L. Phillips, D. H. (1996). Identification of the major tamoxifen-deoxyguanosine adduct formed in the liver DNA of rats treated with tamoxifen. Cancer Res 56:66–71.
  • Oscarson, M. (2001). Genetic polymorphisms in the cytochrome P450 2A6 (CYP2A6) gene: implications for interindividual differences in nicotine metabolism. Drug Metab Dispos 29:91–95.
  • Oscarson, M., Gullsten, H., Rautio, A., Bernal, M. L., Sinues, B., Dahl, M. L., Stengard, J. H., Pelkonen, O., Raunio, H. Ingelman-Sundberg, M. (1998). Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. FEBS Lett 438:201–205.
  • Oscarson, M., Hidestrand, M., Johansson, I. Ingelman-Sundberg, M. (1997). A combination of mutations in the CYP2D6*17 (CYP2D6Z) allele causes alterations in enzyme function. Mol Pharmacol 52:1034–1040.
  • Oscarson, M., McLellan, R. A., Asp, V., Ledesma, M., Bernal Ruiz, M. L., Sinues, B., Rautio, A. Ingelman-Sundberg, M. (2002). Characterization of a novel CYP2A7/CYP2A6 hybrid allele (CYP2A6*12) that causes reduced CYP2A6 activity. Hum Mutat 20:275–283.
  • Oscarson, M., McLellan, R. A., Gullsten, H., Agundez, J. A., Benitez, J., Rautio, A., Raunio, H., Pelkonen, O. Ingelman-Sundberg, M. (1999a). Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. FEBS Lett 460:321–327.
  • Oscarson, M., McLellan, R. A., Gullsten, H., Yue, Q. Y., Lang, M. A., Bernal, M. L., Sinues, B., Hirvonen, A., Raunio, H., Pelkonen, O. Ingelman-Sundberg, M. (1999b). Characterisation and PCR-based detection of a CYP2A6 gene deletion found at a high frequency in a Chinese population. FEBS Lett 448:105–110.
  • Osikowska-Evers, B., Dayer, P., Meyer, U. A., Robertz, G. M. Eichelbaum, M. (1987). Evidence for altered catalytic properties of the cytochrome P-450 involved in sparteine oxidation in poor metabolizers. Clin Pharmacol Ther 41:320–325.
  • Otton, S. V., Ball, S. E., Cheung, S. W., Inaba, T., Rudolph, R. L. Sellers, E. M. (1996). Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol 41:149–156.
  • Otton, S. V., Crewe, H. K., Lennard, M. S., Tucker, G. T. Woods, H. F. (1988). Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P450 in metoprolol oxidation by human liver microsomes. J Pharmacol Exp Ther 247:242–247.
  • Ou-Yang, D. S., Huang, S. L., Wang, W., Xie, H. G., Xu, Z. H., Shu, Y. Zhou, H. H. (2000). Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population. Br J Clin Pharmacol 49:145–151.
  • Owen, A., Pirmohamed, M., Khoo, S. H. Back, D. J. (2006). Pharmacogenetics of HIV therapy. Pharmacogenet Genomics 16:693–703.
  • Ozaki, H., Ishikawa, C. T., Ishii, T., Toyoda, A., Murano, T., Miyashita, Y. Shirai, K. (2005). Clearance rates of cerivastatin metabolites in a patient with cerivastatin-induced rhabdomyolysis. J Clin Pharm Ther 30:189–192.
  • Ozdemir, V., Bertilsson, L., Miura, J., Carpenter, E., Reist, C., Harper, P., Widen, J., Svensson, J. O., Albers, L. J., Kennedy, J. L., Endrenyi, L. Kalow, W. (2007). CYP2D6 genotype in relation to perphenazine concentration and pituitary pharmacodynamic tissue sensitivity in Asians: CYP2D6-serotonin-dopamine crosstalk revisited. Pharmacogenet Genomics 17:339–347.
  • Ozdemir, V., Kalow, W., Okey, A. B., Lam, M. S., Albers, L. J., Reist, C., Fourie, J., Posner, P., Collins, E. J. Roy, R. (2001). Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C–>A polymorphism in intron 1 of the CYP1A2 gene: effect of grapefruit juice and low-dose fluvoxamine. J Clin Psychopharmacol 21:603–607.
  • Ozdemir, V., Naranjo, C. A., Herrmann, N., Reed, K., Sellers, E. M. Kalow, W. (1997). Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo. Clin Pharmacol Ther 62:334–347.
  • Ozdemir, V., Tyndale, R. F., Reed, K., Herrmann, N., Sellers, E. M., Kalow, W. Naranjo, C. A. (1999). Paroxetine steady-state plasma concentration in relation to CYP2D6 genotype in extensive metabolizers. J Clin Psychopharmacol 19:472–475.
  • Paar, W. D., Poche, S., Gerloff, J. Dengler, H. J. (1997). Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol. Eur J Clin Pharmacol 53:235–239.
  • Pai, H. V., Kommaddi, R. P., Chinta, S. J., Mori, T., Boyd, M. R. Ravindranath, V. (2004). A frameshift mutation and alternate splicing in human brain generate a functional form of the pseudogene cytochrome P4502D7 that demethylates codeine to morphine. J Biol Chem 279:27383–27389.
  • Pai, V. B. Nahata, M. C. (1999). Nelfinavir mesylate: a protease inhibitor. Ann Pharmacother 33:325–339.
  • Paine, M. F., Hart, H. L., Ludington, S. S., Haining, R. L., Rettie, A. E. Zeldin, D. C. (2006). The human intestinal cytochrome P450 “pie”. Drug Metab Dispos 34:880–886.
  • Paine, M. F., Khalighi, M., Fisher, J. M., Shen, D. D., Kunze, K. L., Marsh, C. L., Perkins, J. D. Thummel, K. E. (1997). Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 283:1552–1562.
  • Paine, M. F., Schmiedlin-Ren, P. Watkins, P. B. (1999). Cytochrome P-450 1A1 expression in human small bowel: interindividual variation and inhibition by ketoconazole. Drug Metab Dispos 27:360–364.
  • Palovaara, S., Pelkonen, O., Uusitalo, J., Lundgren, S. Laine, K. (2003). Inhibition of cytochrome P450 2B6 activity by hormone replacement therapy and oral contraceptive as measured by bupropion hydroxylation. Clin Pharmacol Ther 74:326–333.
  • Pan, L., Vander Stichele, R., Rosseel, M. T., Berlo, J. A., De Schepper, N., Belpaire, F. M. (1999). Effects of smoking, CYP2D6 genotype, and concomitant drug intake on the steady-state plasma concentrations of haloperidol and reduced haloperidol in schizophrenic inpatients. Ther Drug Monit 21:489–497.
  • Pan, L. P., De Vriendt, C., Belpaire, F. M. (1998). In-vitro characterization of the cytochrome P450 isoenzymes involved in the back oxidation and N-dealkylation of reduced haloperidol. Pharmacogenetics 8:383–389.
  • Panserat, S., Mura, C., Gerard, N., Vincent-Viry, M., Galteau, M. M., Jacoz-Aigrain, E. Krishnamoorthy, R. (1995). An unequal cross-over event within the CYP2D gene cluster generates a chimeric CYP2D7/CYP2D6 gene which is associated with the poor metabolizer phenotype. Br J Clin Pharmacol 40:361–367.
  • Panserat, S., Mura, C., Gerard, N., Vincent-Viry, M., Galteau, M. M., Jacqz-Aigrain, E. Krishnamoorthy, R. (1994). DNA haplotype-dependent differences in the amino acid sequence of debrisoquine 4-hydroxylase (CYP2D6): evidence for two major allozymes in extensive metabolisers. Hum Genet 94:401–406.
  • Papadopoulos, A. S., Crammer, J. L. Cowan, D. A. (1985). Phenolic metabolites of thioridazine in man. Xenobiotica 15:309–316.
  • Paris, P. L., Kupelian, P. A., Hall, J. M., Williams, T. L., Levin, H., Klein, E. A., Casey, G. Witte, J. S. (1999). Association between a CYP3A4 genetic variant and clinical presentation in African-American prostate cancer patients. Cancer Epidemiol Biomarkers Prev 8:901–905.
  • Park, S. B., Jacob, P., 3rd, Benowitz, N. L. Cashman, J. R. (1993). Stereoselective metabolism of (S)-(-)-nicotine in humans: formation of trans-(S)-(-)-nicotine N-1’-oxide. Chem Res Toxicol 6:880–888.
  • Parker, J. C. (2002). Troglitazone: the discovery and development of a novel therapy for the treatment of type 2 diabetes mellitus. Adv Drug Deliv Rev 54:1173–1197.
  • Parmeggiani, A., Posar, A., Sangiorgi, S. Giovanardi-Rossi, P. (2004). Unusual side effects due to clobazam: a case report with genetic study of CYP2C19. Brain Dev 26: 63–66.
  • Parte, P. Kupfer, D. (2005). Oxidation of tamoxifen by human flavin-containing monooxygenase (FMO) 1 and FMO3 to tamoxifen-N-oxide and its novel reduction back to tamoxifen by human cytochromes P450 and hemoglobin. Drug Metab Dispos 33:1446–1452.
  • Pasanen, M., Rannala, Z., Tooming, A., Sotaniemi, E. A., Pelkonen, O. Rautio, A. (1997). Hepatitis A impairs the function of human hepatic CYP2A6 in vivo. Toxicology 123:177–184.
  • Patel, B. K., Jackson, S. H., Swift, C. G. Hutt, A. J. (2003). Disposition of flurbiprofen in man: influence of stereochemistry and age. Xenobiotica 33:1043–1057.
  • Pathak, D. N., Pongracz, K. Bodell, W. J. (1996). Activation of 4-hydroxytamoxifen and the tamoxifen derivative metabolite E by uterine peroxidase to form DNA adducts: comparison with DNA adducts formed in the uterus of Sprague-Dawley rats treated with tamoxifen. Carcinogenesis 17:1785–1790.
  • Patki, K. C., Von Moltke, L. L. Greenblatt, D. J. (2003). In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes p450: role of cyp3a4 and cyp3a5. Drug Metab Dispos 31:938–944.
  • Patten, C. J., Smith, T. J., Friesen, M. J., Tynes, R. E., Yang, C. S. Murphy, S. E. (1997). Evidence for cytochrome P450 2A6 and 3A4 as major catalysts for N’-nitrosonornicotine alpha-hydroxylation by human liver microsomes. Carcinogenesis 18: 1623–1630.
  • Patten, C. J., Smith, T. J., Murphy, S. E., Wang, M. H., Lee, J., Tynes, R. E., Koch, P. Yang, C. S. (1996). Kinetic analysis of the activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone by heterologously expressed human P450 enzymes and the effect of P450-specific chemical inhibitors on this activation in human liver microsomes. Arch Biochem Biophys 333:127–138.
  • Paulson, S. K., Hribar, J. D., Liu, N. W., Hajdu, E., Bible, R. H., Jr., Piergies, A. Karim, A. (2000). Metabolism and excretion of [(14)C]celecoxib in healthy male volunteers. Drug Metab Dispos 28:308–314.
  • Paulussen, A., Lavrijsen, K., Bohets, H., Hendrickx, J., Verhasselt, P., Luyten, W., Konings, F. Armstrong, M. (2000). Two linked mutations in transcriptional regulatory elements of the CYP3A5 gene constitute the major genetic determinant of polymorphic activity in humans. Pharmacogenetics 10:415–424.
  • Pavanello, S., B’Chir, F., Pulliero, A., Saguem, S., Ben Fraj, R., El Aziz Hayouni, A., Clonfero, E., Mastrangelo, G. (2007). Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung. Lung Cancer 57:266–272.
  • Peamkrasatam, S., Sriwatanakul, K., Kiyotani, K., Fujieda, M., Yamazaki, H., Kamataki, T. Yoovathaworn, K. (2006). In vivo evaluation of coumarin and nicotine as probe drugs to predict the metabolic capacity of CYP2A6 due to genetic polymorphism in Thais. Drug Metab Pharmacokinet 21:475–484.
  • Pearce, R. E., Rodrigues, A. D., Goldstein, J. A. Parkinson, A. (1996). Identification of the human P450 enzymes involved in lansoprazole metabolism. J Pharmacol Exp Ther 277:805–816.
  • Pedersen, R. S., Damkier, P. Brosen, K. (2005). Tramadol as a new probe for cytochrome P450 2D6 phenotyping: a population study. Clin Pharmacol Ther 77:458–467.
  • Pedersen, R. S., Damkier, P. Brosen, K. (2006a). The effects of human CYP2C8 genotype and fluvoxamine on the pharmacokinetics of rosiglitazone in healthy subjects. Br J Clin Pharmacol 62:682–689.
  • Pedersen, R. S., Damkier, P. Brosen, K. (2006b). Enantioselective pharmacokinetics of tramadol in CYP2D6 extensive and poor metabolizers. Eur J Clin Pharmacol 62:513–521.
  • Peets, E. A., Weinstein, R., Billard, W. Symchowicz, S. (1972). The metabolism of chlorpheniramine maleate in the dog and rat. Arch Int Pharmacodyn Ther 199:172–190.
  • Pelkonen, O., Rautio, A., Raunio, H. Pasanen, M. (2000). CYP2A6: a human coumarin 7-hydroxylase. Toxicology 144:139–147.
  • Penman, B. W., Chen, L., Gelboin, H. V., Gonzalez, F. J. Crespi, C. L. (1994). Development of a human lymphoblastoid cell line constitutively expressing human CYP1A1 cDNA: substrate specificity with model substrates and promutagens. Carcinogenesis 15:1931–1937.
  • Penzak, S. R., Kabuye, G., Mugyenyi, P., Mbamanya, F., Natarajan, V., Alfaro, R. M., Kityo, C., Formentini, E. Masur, H. (2007). Cytochrome P450 2B6 (CYP2B6) G516T influences nevirapine plasma concentrations in HIV-infected patients in Uganda. HIV Med 8:86–91.
  • Perera, F. P., Jedrychowski, W., Rauh, V. Whyatt, R. M. (1999). Molecular epidemiologic research on the effects of environmental pollutants on the fetus. Environ Health Perspect 107 (Supp l3):451–460.
  • Perini, J. A., Vianna-Jorge, R., Brogliato, A. R. Suarez-Kurtz, G. (2005). Influence of CYP2C9 genotypes on the pharmacokinetics and pharmacodynamics of piroxicam. Clin Pharmacol Ther 78:362–369.
  • Perloff, M. D., von Moltke, L. L., Court, M. H., Kotegawa, T., Shader, R. I. Greenblatt, D. J. (2000). Midazolam and triazolam biotransformation in mouse and human liver microsomes: relative contribution of CYP3A and CYP2C isoforms. J Pharmacol Exp Ther 292:618–628.
  • Perrier, L., Bourrie, M., Marti, E., Tronquet, C., Masse, D., Berger, Y., Magdalou, J. Fabre, G. (1994). In vitro N-glucuronidation of SB 47436 (BMS 186295), a new AT1 nonpeptide angiotensin II receptor antagonist, by rat, monkey, and human hepatic microsomal fractions. J Pharmacol Exp Ther 271:91–99.
  • Persson, I., Johansson, I. Ingelman-Sundberg, M. (1997). In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility. Biochem Biophys Res Commun 231:227–230.
  • Peters, E. J., Slager, S. L., Kraft, J. B., Jenkins, G. D., Reinalda, M. S., McGrath, P. J. Hamilton, S. P. (2008). Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS ONE 3:e1872.
  • Petersen, D. D., McKinney, C. E., Ikeya, K., Smith, H. H., Bale, A. E., McBride, O. W. Nebert, D. W. (1991). Human CYP1A1 gene: cosegregation of the enzyme inducibility phenotype and an RFLP. Am J Hum Genet 48:720–725.
  • Pfutzner, A., Schneider, C. A. Forst, T. (2006). Pioglitazone: an antidiabetic drug with cardiovascular therapeutic effects. Expert Rev Cardiovasc Ther 4:445–459.
  • Phillips, D. H., Carmichael, P. L., Hewer, A., Cole, K. J. Poon, G. K. (1994). alpha-hydroxytamoxifen, a metabolite of tamoxifen with exceptionally high DNA-binding activity in rat hepatocytes. Cancer Res 54:5518–5522.
  • Pianezza, M. L., Sellers, E. M. Tyndale, R. F. (1998). Nicotine metabolism defect reduces smoking. Nature 393:750.
  • Picard, N., Cresteil, T., Djebli, N. Marquet, P. (2005). In vitro metabolism study of buprenorphine: evidence for new metabolic pathways. Drug Metab Dispos 33:689–695.
  • Pilotto, A., Seripa, D., Franceschi, M., Scarcelli, C., Colaizzo, D., Grandone, E., Niro, V., Andriulli, A., Leandro, G., Di Mario F., Dallapiccola, B. (2007). Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology 133:465–471.
  • Pinder, R. M. Van Delft, A. M. (1983). The potential therapeutic role of the enantiomers and metabolites of mianserin. Br J Clin Pharmacol 15(Suppl 2):269S–276S.
  • Pinto, A. G., Wang, Y. H., Chalasani, N., Skaar, T., Kolwankar, D., Gorski, J. C., Liangpunsakul, S., Hamman, M. A., Arefayene, M. Hall, S. D. (2005). Inhibition of human intestinal wall metabolism by macrolide antibiotics: effect of clarithromycin on cytochrome P450 3A4/5 activity and expression. Clin Pharmacol Ther 77:178–188.
  • Pinzani, V., Faucherre, V., Peyriere, H. Blayac, J. P. (2000). Methadone withdrawal symptoms with nevirapine and efavirenz. Ann Pharmacother 34:405–407.
  • Pitarque, M., von Richter, O., Oke, B., Berkkan, H., Oscarson, M., Ingelman-Sundberg, M. (2001). Identification of a single-nucleotide polymorphism in the TATA box of the CYP2A6 gene: impairment of its promoter activity. Biochem Biophys Res Commun 284:455–460.
  • Pitarque, M., von Richter, O., Rodriguez-Antona, C., Wang, J., Oscarson, M., Ingelman-Sundberg, M. (2004). A nicotine C-oxidase gene (CYP2A6) polymorphism important for promoter activity. Hum Mutat 23:258–266.
  • Pittas, A. G. Greenberg, A. S. (2002). Thiazolidinediones in the treatment of type 2 diabetes. Expert Opin Pharmacother 3:529–540.
  • Pollock, B. G., Mulsant, B. H., Sweet, R. A., Rosen, J., Altieri, L. P. Perel, J. M. (1995). Prospective cytochrome P450 phenotyping for neuroleptic treatment in dementia. Psychopharmacol Bull 31:327–331.
  • Poon, G. K., Chui, Y. C., McCague, R., Llnning, P. E., Feng, R., Rowlands, M. G. Jarman, M. (1993). Analysis of phase I and phase II metabolites of tamoxifen in breast cancer patients. Drug Metab Dispos 21:1119–1124.
  • Poulsen, L., Arendt-Nielsen, L., Brosen, K. Sindrup, S. H. (1996a). The hypoalgesic effect of tramadol in relation to CYP2D6. Clin Pharmacol Ther 60:636–644.
  • Poulsen, L., Brosen, K., Arendt-Nielsen, L., Gram, L. F., Elbaek, K. Sindrup, S. H. (1996b). Codeine and morphine in extensive and poor metabolizers of sparteine: pharmacokinetics, analgesic effect, and side effects. Eur J Clin Pharmacol 51:289–295.
  • Projean, D., Morin, P. E., Tu, T. M. Ducharme, J. (2003). Identification of CYP3A4 and CYP2C8 as the major cytochrome P 450 s responsible for morphine N-demethylation in human liver microsomes. Xenobiotica 33:841–854.
  • Prueksaritanont, T., Dwyer, L. M. Cribb, A. E. (1995). (+)-bufuralol 1’-hydroxylation activity in human and rhesus monkey intestine and liver. Biochem Pharmacol 50:1521–1525.
  • Prueksaritanont, T., Gorham, L. M., Hochman, J. H., Tran, L. O. Vyas, K. P. (1996). Comparative studies of drug-metabolizing enzymes in dog, monkey, and human small intestines, and in Caco-2 cells. Drug Metab Dispos 24:634–642.
  • Prueksaritanont, T., Gorham, L. M., Ma, B., Liu, L., Yu, X., Zhao, J. J., Slaughter, D. E., Arison, B. H. Vyas, K. P. (1997). In vitro metabolism of simvastatin in humans [SBT]identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 25:1191–1199.
  • Prueksaritanont, T., Ma, B. Yu, N. (2003). The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. Br J Clin Pharmacol 56:120–124.
  • Prueksaritanont, T., Subramanian, R., Fang, X., Ma, B., Qiu, Y., Lin, J. H., Pearson, P. G. Baillie, T. A. (2002). Glucuronidation of statins in animals and humans: a novel mechanism of statin lactonization. Drug Metab Dispos 30:505–512.
  • Purkins, L., Wood, N., Ghahramani, P., Greenhalgh, K., Allen, M. J. Kleinermans, D. (2002). Pharmacokinetics and safety of voriconazole following intravenous-to-oral-dose escalation regimens. Antimicrob Agents Chemother 46:2546–2553.
  • Qin, X. P., Xie, H. G., Wang, W., He, N., Huang, S. L., Xu, Z. H., Ou-Yang, D. S., Wang, Y. J. Zhou, H. H. (1999). Effect of the gene dosage of CgammaP2C19 on diazepam metabolism in Chinese subjects. Clin Pharmacol Ther 66:642–646.
  • Quattrochi, L. C. Tukey, R. H. (1989). The human cytochrome Cyp1A2 gene contains regulatory elements responsive to 3-methylcholanthrene. Mol Pharmacol 36:66–71.
  • Quinn, M. J. Fitzgerald, D. J. (1999). Ticlopidine and clopidogrel. Circulation 100:1667–1672.
  • Radunovic, A., Mitsumoto, H. Leigh, P. N. (2007). Clinical care of patients with amyotrophic lateral sclerosis. Lancet Neurol 6:913–925.
  • Rahman, A., Korzekwa, K. R., Grogan, J., Gonzalez, F. J. Harris, J. W. (1994). Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 54:5543–5546.
  • Raimundo, S., Fischer, J., Eichelbaum, M., Griese, E. U., Schwab, M. Zanger, U. M. (2000). Elucidation of the genetic basis of the common “intermediate metabolizer” phenotype for drug oxidation by CYP2D6. Pharmacogenetics 10: 577–581.
  • Raimundo, S., Toscano, C., Klein, K., Fischer, J., Griese, E. U., Eichelbaum, M., Schwab, M. Zanger, U. M. (2004). A novel intronic mutation, 2988G>A, with high predictivity for impaired function of cytochrome P450 2D6 in white subjects. Clin Pharmacol Ther 76:128–138.
  • Ramamoorthy, Y., Tyndale, R. F. Sellers, E. M. (2001). Cytochrome P450 2D6.1 and cytochrome P450 2D6.10 differ in catalytic activity for multiple substrates. Pharmacogenetics 11:477–487.
  • Ramanathan, R., Reyderman, L., Kulmatycki, K., Su, A. D., Alvarez, N., Chowdhury, S. K., Alton, K. B., Wirth, M. A., Clement, R. P., Statkevich, P. Patrick, J. E. (2007a). Disposition of loratadine in healthy volunteers. Xenobiotica 37:753–769.
  • Ramanathan, R., Reyderman, L., Su, A. D., Alvarez, N., Chowdhury, S. K., Alton, K. B., Wirth, M. A., Clement, R. P., Statkevich, P. Patrick, J. E. (2007b). Disposition of desloratadine in healthy volunteers. Xenobiotica 37:770–787.
  • Ramirez, J., Innocenti, F., Schuetz, E. G., Flockhart, D. A., Relling, M. V., Santucci, R. Ratain, M. J. (2004). CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes. Drug Metab Dispos 32:930–936.
  • Raney, K. D., Meyer, D. J., Ketterer, B., Harris, T. M. Guengerich, F. P. (1992). Glutathione conjugation of aflatoxin B1 exo- and endo-epoxides by rat and human glutathione S-transferases. Chem Res Toxicol 5:470–478.
  • Rao, N. (2007). The clinical pharmacokinetics of escitalopram. Clin Pharmacokinet 46:281–290.
  • Rao, Y., Hoffmann, E., Zia, M., Bodin, L., Zeman, M., Sellers, E. M. Tyndale, R. F. (2000). Duplications and defects in the CYP2A6 gene: identification, genotyping, and in vivo effects on smoking. Mol Pharmacol 58:747–755.
  • Raskind, M. A., Peskind, E. R., Wessel, T. Yuan, W. (2000). Galantamine in AD: A 6-month randomized, placebo-controlled trial with a 6-month extension. The Galantamine USA-1 Study Group. Neurology 54:2261–2268.
  • Rasmussen, B. B., Brix, T. H., Kyvik, K. O. Brosen, K. (2002). The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors. Pharmacogenetics 12:473–478.
  • Rau, T., Diepenbruck, S., Diepenbruck, I. Eschenhagen, T. (2006). The 2988G>A polymorphism affects splicing of a CYP2D6 minigene. Clin Pharmacol Ther 80:555–558; author reply, 558-560.
  • Rau, T., Wohlleben, G., Wuttke, H., Thuerauf, N., Lunkenheimer, J., Lanczik, M. Eschenhagen, T. (2004). CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants-a pilot study. Clin Pharmacol Ther 75:386–393.
  • Raunio, H., Rautio, A. Pelkonen, O. (1999). The CYP2A subfamily: function, expression, and genetic polymorphism. IARC Sci Publ: 148:197–207.
  • Rautio, A., Kraul, H., Kojo, A., Salmela, E. Pelkonen, O. (1992). Interindividual variability of coumarin 7-hydroxylation in healthy volunteers. Pharmacogenetics 2:227–233.
  • Ravindran, S., Zharikova, O. L., Hill, R. A., Nanovskaya, T. N., Hankins, G. D. Ahmed, M. S. (2006). Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons. Biochem Pharmacol 72:1730–1737.
  • Ray, W. J., Bain, G., Yao, M. Gottlieb, D. I. (1997). CYP26, a novel mammalian cytochrome P450, is induced by retinoic acid and defines a new family. J Biol Chem 272:18702–18708.
  • Rebbeck, T. R., Jaffe, J. M., Walker, A. H., Wein, A. J. Malkowicz, S. B. (1998). Modification of clinical presentation of prostate tumours by a novel genetic variant in CYP3A4. J Natl Cancer Inst 90:1225–1229.
  • Reese, M. J., Wurm, R. M., Muir, K. T., Generaux, G. T., St John-Williams, L., McConn, D. J. (2008). An in vitro mechanistic study to elucidate the desipramine/bupropion clinical drug-drug interaction. Drug Metab Dispos 36:1198–1201.
  • Rehmel, J. L., Eckstein, J. A., Farid, N. A., Heim, J. B., Kasper, S. C., Kurihara, A., Wrighton, S. A. Ring, B. J. (2006). Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab Dispos 34:600–607.
  • Relling, M. V., Lin, J. S., Ayers, G. D. Evans, W. E. (1992). Racial and gender differences in N-acetyltransferase, xanthine oxidase, and CYP1A2 activities. Clin Pharmacol Ther 52:643–658.
  • Renberg, L., Simonsson, R. Hoffmann, K. J. (1989). Identification of two main urinary metabolites of [14C]omeprazole in humans. Drug Metab Dispos 17:69–76.
  • Rendic, S. Di Carlo, F. J. (1997). Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 29:413–580.
  • Rengelshausen, J., Banfield, M., Riedel, K. D., Burhenne, J., Weiss, J., Thomsen, T., Walter-Sack, I., Haefeli, W. E. Mikus, G. (2005). Opposite effects of short-term and long-term St John’s wort intake on voriconazole pharmacokinetics. Clin Pharmacol Ther 78:25–33.
  • Rettie, A. E. Jones, J. P. (2005). Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics. Annu Rev Pharmacol Toxicol 45:477–494.
  • Rettie, A. E., Wienkers, L. C., Gonzalez, F. J., Trager, W. F. Korzekwa, K. R. (1994). Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics 4:39–42.
  • Ribaudo, H. J., Haas, D. W., Tierney, C., Kim, R. B., Wilkinson, G. R., Gulick, R. M., Clifford, D. B., Marzolini, C., Fletcher, C. V., Tashima, K. T., Kuritzkes, D. R. Acosta, E. P. (2006). Pharmacogenetics of plasma efavirenz exposure after treatment discontinuation: an Adult AIDS Clinical Trials Group Study. Clin Infect Dis 42:401–407.
  • Ribera, E., Pou, L., Lopez, R. M., Crespo, M., Falco, V., Ocana, I., Ruiz, I. Pahissa, A. (2001). Pharmacokinetic interaction between nevirapine and rifampicin in HIV-infected patients with tuberculosis. J Acquir Immune Defic Syndr 28:450–453.
  • Richardson, T. H., Jung, F., Griffin, K. J., Wester, M., Raucy, J. L., Kemper, B., Bornheim, L. M., Hassett, C., Omiecinski, C. J. Johnson, E. F. (1995). A universal approach to the expression of human and rabbit cytochrome P450s of the 2C subfamily in Escherichia coli. Arch Biochem Biophys 323:87–96.
  • Richelson, E. Nelson, A. (1984). Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol 103:197–204.
  • Riemersma-van der Lek, R. F., Swaab, D. F., Twisk, J., Hol, E. M., Hoogendijk, W. J. Van Someren, E. J. (2008). Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized, controlled trial. JAMA 299:2642–2655.
  • Rifkind, A. B., Lee, C., Chang, T. K. Waxman, D. J. (1995). Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2: regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes. Arch Biochem Biophys 320:380–389.
  • Riley, A. B., Tafreshi, M. J. Haber, S. L. (2008). Prasugrel: a novel antiplatelet agent. Am J Health Syst Pharm 65:1019–1028.
  • Ring, B. J., Catlow, J., Lindsay, T. J., Gillespie, T., Roskos, L. K., Cerimele, B. J., Swanson, S. P., Hamman, M. A. Wrighton, S. A. (1996). Identification of the human cytochromes P450 responsible for the in vitro formation of the major oxidative metabolites of the antipsychotic agent olanzapine. J Pharmacol Exp Ther 276:658–666.
  • Ring, B. J., Eckstein, J. A., Gillespie, J. S., Binkley, S. N., VandenBranden, M. Wrighton, S. A. (2001). Identification of the human cytochromes p450 responsible for in vitro formation of R- and S-norfluoxetine. J Pharmacol Exp Ther 297:1044–1050.
  • Risdall, P. C., Adams, S. S., Crampton, E. L. Marchant, B. (1978). The disposition and metabolism of flurbiprofen in several species including man. Xenobiotica 8:691–703.
  • Riska, P., Lamson, M., MacGregor, T., Sabo, J., Hattox, S., Pav, J. Keirns, J. (1999). Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab Dispos 27:895–901.
  • Rittenbach, K. A., Holt, A., Ling, L., Shan, J. Baker, G. B. (2007). Metabolism of N-methyl, N-propargylphenylethylamine: studies with human liver microsomes and cDNA expressed cytochrome P450 (CYP) enzymes. Cell Mol Neurobiol 27:179–190.
  • Roberts, R. L., Luty, S. E., Mulder, R. T., Joyce, P. R. Kennedy, M. A. (2004a). Association between cytochrome P450 2D6 genotype and harm avoidance. Am J Med Genet B Neuropsychiatr Genet 127B:90–93.
  • Roberts, R. L., Mulder, R. T., Joyce, P. R., Luty, S. E. Kennedy, M. A. (2004b). No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline. Hum Psychopharmacol 19:17–23.
  • Robertson, I. G., Guthenberg, C., Mannervik, B. Jernstrom, B. (1986). Differences in stereoselectivity and catalytic efficiency of three human glutathione transferases in the conjugation of glutathione with 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. Cancer Res 46:2220–2224.
  • Rochat, B., Amey, M. Baumann, P. (1995). Analysis of enantiomers of citalopram and its demethylated metabolites in plasma of depressive patients using chiral reverse-phase liquid chromatography. Ther Drug Monit 17:273–279.
  • Rochat, B., Amey, M., Gillet, M., Meyer, U. A. Baumann, P. (1997). Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmacogenetics 7:1–10.
  • Roden, D. M., Duff, H. J., Altenbern, D. Woosley, R. L. (1982). Antiarrhythmic activity of the O-demethyl metabolite of encainide. J Pharmacol Exp Ther 221:552–557.
  • Roden, D. M., Wood, A. J., Wilkinson, G. R. Woosley, R. L. (1986). Disposition kinetics of encainide and metabolites. Am J Cardiol 58:4C–9C.
  • Roden, D. M. Woosley, R. L. (1988). Clinical pharmacokinetics of encainide. Clin Pharmacokinet 14:141–147.
  • Rodrigues, A. D. (2005). Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same? Drug Metab Dispos 33:1567–1575.
  • Rodriguez-Antona, C., Niemi, M., Backman, J. T., Kajosaari, L. I., Neuvonen, P. J., Robledo, M. Ingelman-Sundberg, M. (2008). Characterization of novel CYP2C8 haplotypes and their contribution to paclitaxel and repaglinide metabolism. Pharmacogenomics J 8:268–277.
  • Rodriguez-Antona, C., Niemi, M., Backman, J. T., Kajosaari, L. I., Neuvonen, P. J., Robledo, M. Ingelman-Sundberg, M. (2008). Characterization of novel CYP2C8 haplotypes and their contribution to paclitaxel and repaglinide metabolism. Pharmacogenomics J 8:268–277.
  • Rodriguez-Novoa, S., Barreiro, P., Rendon, A., Jimenez-Nacher, I., Gonzalez-Lahoz, J. Soriano, V. (2005). Influence of 516G>T polymorphisms at the gene encoding the CYP450-2B6 isoenzyme on efavirenz plasma concentrations in HIV-infected subjects. Clin Infect Dis 40:1358–1361.
  • Roh, H. K., Chung, J. Y., Oh, D. Y., Park, C. S., Svensson, J. O., Dahl, M. L. Bertilsson, L. (2001a). Plasma concentrations of haloperidol are related to CYP2D6 genotype at low, but not high doses of haloperidol in Korean schizophrenic patients. Br J Clin Pharmacol 52:265–271.
  • Roh, H. K., Kim, C. E., Chung, W. G., Park, C. S., Svensson, J. O. Bertilsson, L. (2001b). Risperidone metabolism in relation to CYP2D6*10 allele in Korean schizophrenic patients. Eur J Clin Pharmacol 57:671–675.
  • Romkes, M., Faletto, M. B., Blaisdell, J. A., Raucy, J. L. Goldstein, J. A. (1991). Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. Biochemistry 30:3247–3255.
  • Roos, W., Oeze, L., Loser, R. Eppenberger, U. (1983). Antiestrogenic action of 3-hydroxytamoxifen in the human breast cancer cell line MCF-7. J Natl Cancer Inst 71:55–59.
  • Rooseboom, M., Commandeur, J. N. Vermeulen, N. P. (2004). Enzyme-catalyzed activation of anticancer prodrugs. Pharmacol Rev 56:53–102.
  • Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O’Regan, J. P., Deng, H. X. et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62.
  • Ross, R. K., Pike, M. C., Coetzee, G. A., Reichardt, J. K., Yu, M. C., Feigelson, H., Stanczyk, F. Z., Kolonel, L. N. Henderson, B. E. (1998). Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Res 58:4497–4504.
  • Rossini, A., de Almeida Simao, T., Albano, R. M. Pinto, L. F. (2008). CYP2A6 polymorphisms and risk for tobacco-related cancers. Pharmacogenomics 9:1737–1752.
  • Rost, S., Fregin, A., Ivaskevicius, V., Conzelmann, E., Hortnagel, K., Pelz, H. J., Lappegard, K., Seifried, E., Scharrer, I., Tuddenham, E. G., Muller, C. R., Strom, T. M. Oldenburg, J. (2004). Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature 427:537–541.
  • Rotger, M., Colombo, S., Furrer, H., Bleiber, G., Buclin, T., Lee, B. L., Keiser, O., Biollaz, J., Decosterd, L. Telenti, A. (2005). Influence of CYP2B6 polymorphism on plasma and intracellular concentrations and toxicity of efavirenz and nevirapine in HIV-infected patients. Pharmacogenet Genomics 15:1–5.
  • Rotger, M., Saumoy, M., Zhang, K., Flepp, M., Sahli, R., Decosterd, L. Telenti, A. (2007a). Partial deletion of CYP2B6 owing to unequal crossover with CYP2B7. Pharmacogenet Genomics 17:885–890.
  • Rotger, M., Tegude, H., Colombo, S., Cavassini, M., Furrer, H., Decosterd, L., Blievernicht, J., Saussele, T., Gunthard, H. F., Schwab, M., Eichelbaum, M., Telenti, A. Zanger, U. M. (2007b). Predictive value of known and novel alleles of CYP2B6 for efavirenz plasma concentrations in HIV-infected individuals. Clin Pharmacol Ther 81:557–566.
  • Rotzinger, S., Fang, J. Baker, G. B. (1998). Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos 26:572–575.
  • Rowland, P., Blaney, F. E., Smyth, M. G., Jones, J. J., Leydon, V. R., Oxbrow, A. K., Lewis, C. J., Tennant, M. G., Modi, S., Eggleston, D. S., Chenery, R. J. Bridges, A. M. (2006). Crystal structure of human cytochrome P450 2D6. J Biol Chem 281:7614–7622.
  • Rozman, B. (2002). Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet 41:421–430.
  • Rudberg, I., Mohebi, B., Hermann, M., Refsum, H. Molden, E. (2008). Impact of the ultrarapid CYP2C19*17 allele on serum concentration of escitalopram in psychiatric patients. Clin Pharmacol Ther 83:322–327.
  • Rudy, A. C., Knight, P. M., Brater, D. C. Hall, S. D. (1991). Stereoselective metabolism of ibuprofen in humans: administration of R-, S-, and racemic ibuprofen. J Pharmacol Exp Ther 259:1133–1139.
  • Ruenitz, P. C., Bagley, J. R. Mokler, C. M. (1982). Estrogenic and antiestrogenic activity of monophenolic analogues of tamoxifen, (Z)-2-[p-(1,2-diphenyl-1-butenyl)phenoxy]-N, N-dimethylethylamine. J Med Chem 25:1056–1060.
  • Ruenitz, P. C., Bagley, J. R. Pape, C. W. (1984). Some chemical and biochemical aspects of liver microsomal metabolism of tamoxifen. Drug Metab Dispos 12:478–483.
  • Ruiz, N. (1999). Clinical history of efavirenz. Int J Clin Pract Suppl 103:3–7.
  • Rydberg, T., Jonsson, A. Melander, A. (1995). Comparison of the kinetics of glyburide and its active metabolites in humans. J Clin Pharm Ther 20:283–295.
  • Rydberg, T., Jonsson, A., Roder, M. Melander, A. (1994). Hypoglycemic activity of glyburide (glibenclamide) metabolites in humans. Diabetes Care 17:1026–1030.
  • Sachse, C., Brockmoller, J., Bauer, S., Reum, T. Roots, I. (1996). A rare insertion of T226 in exon 1 of CYP2D6 causes a frameshift and is associated with the poor metabolizer phenotype: CYP2D6*15. Pharmacogenetics 6:269–272.
  • Sachse, C., Brockmoller, J., Bauer, S. Roots, I. (1997). Cytochrome P450 2D6 variants in a Caucasian population: allele frequencies and phenotypic consequences. Am J Hum Genet 60:284–295.
  • Sachse, C., Brockmoller, J., Bauer, S. Roots, I. (1999). Functional significance of a C–>A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine. Br J Clin Pharmacol 47:445–449.
  • Sachse, C., Brockmoller, J., Hildebrand, M., Muller, K. Roots, I. (1998). Correctness of prediction of the CYP2D6 phenotype confirmed by genotyping 47 intermediate and poor metabolizers of debrisoquine. Pharmacogenetics 8:181–185.
  • Sadeque, A. J., Fisher, M. B., Korzekwa, K. R., Gonzalez, F. J. Rettie, A. E. (1997). Human CYP2C9 and CYP2A6 mediate formation of the hepatotoxin 4-ene-valproic acid. J Pharmacol Exp Ther 283:698–703.
  • Saeki, M., Saito, Y., Nakamura, T., Murayama, N., Kim, S. R., Ozawa, S., Komamura, K., Ueno, K., Kamakura, S., Nakajima, T., Saito, H., Kitamura, Y., Kamatani, N. Sawada, J. (2003). Single nucleotide polymorphisms and haplotype frequencies of CYP3A5 in a Japanese population. Hum Mutat 21:653–659.
  • Sagar, M., Janczewska, I., Ljungdahl, A., Bertilsson, L. Seensalu, R. (1999). Effect of CYP2C19 polymorphism on serum levels of vitamin B12 in patients on long-term omeprazole treatment. Aliment Pharmacol Ther 13:453–458.
  • Sagar, M., Tybring, G., Dahl, M. L., Bertilsson, L. Seensalu, R. (2000). Effects of omeprazole on intragastric pH and plasma gastrin are dependent on the CYP2C19 polymorphism. Gastroenterology 119:670–676.
  • Saito, S., Iida, A., Sekine, A., Kawauchi, S., Higuchi, S., Ogawa, C. Nakamura, Y. (2003a). Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population. J Hum Genet 48:249–270.
  • Saito, T., Egashira, M., Kiyotani, K., Fujieda, M., Yamazaki, H., Kiyohara, C., Kunitoh, H. Kamataki, T. (2003b). Novel nonsynonymous polymorphisms of the CYP1A1 gene in Japanese. Drug Metab Pharmacokinet 18:218–221.
  • Saito, Y., Hanioka, N., Maekawa, K., Isobe, T., Tsuneto, Y., Nakamura, R., Soyama, A., Ozawa, S., Tanaka-Kagawa, T., Jinno, H., Narimatsu, S. Sawada, J. (2005). Functional analysis of three CYP1A2 variants found in a Japanese population. Drug Metab Dispos 33:1905–1910.
  • Saito, Y., Katori, N., Soyama, A., Nakajima, Y., Yoshitani, T., Kim, S. R., Fukushima-Uesaka, H., Kurose, K., Kaniwa, N., Ozawa, S., Kamatani, N., Komamura, K., Kamakura, S., Kitakaze, M., Tomoike, H., Sugai, K., Minami, N., Kimura, H., Goto, Y., Minami, H., Yoshida, T., Kunitoh, H., Ohe, Y., Yamamoto, N., Tamura, T., Saijo, N. Sawada, J. (2007). CYP2C8 haplotype structures and their influence on pharmacokinetics of paclitaxel in a Japanese population. Pharmacogenet Genomics 17:461–471.
  • Saitoh, A., Sarles, E., Capparelli, E., Aweeka, F., Kovacs, A., Burchett, S. K., Wiznia, A., Nachman, S., Fenton, T. Spector, S. A. (2007). CYP2B6 genetic variants are associated with nevirapine pharmacokinetics and clinical response in HIV-1-infected children. Aids 21:2191–2199.
  • Sakaguchi, K., Green, M., Stock, N., Reger, T. S., Zunic, J. King, C. (2004). Glucuronidation of carboxylic acid containing compounds by UDP-glucuronosyltransferase isoforms. Arch Biochem Biophys 424:219–225.
  • Sakuyama, K., Sasaki, T., Ujiie, S., Obata, K., Mizugaki, M., Ishikawa, M. Hiratsuka, M. (2008). Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57). Drug Metab Dispos 36:2460–2467.
  • Salerno, D. M., Granrud, G., Sharkey, P., Krejci, J., Larson, T., Erlien, D., Berry, D. Hodges, M. (1986). Pharmacodynamics and side effects of flecainide acetate. Clin Pharmacol Ther 40:101–107.
  • Salonen, J. S., Nyman, L., Boobis, A. R., Edwards, R. J., Watts, P., Lake, B. G., Price, R. J., Renwick, A. B., Gomez-Lechon, M. J., Castell, J. V., Ingelman-Sundberg, M., Hidestrand, M., Guillouzo, A., Corcos, L., Goldfarb, P. S., Lewis, D. F., Taavitsainen, P. Pelkonen, O. (2003). Comparative studies on the cytochrome p450-associated metabolism and interaction potential of selegiline between human liver-derived in vitro systems. Drug Metab Dispos 31:1093–1102.
  • Sanchez, R. I., Wang, R. W., Newton, D. J., Bakhtiar, R., Lu, P., Chiu, S. H., Evans, D. C. Huskey, S. E. (2004). Cytochrome P450 3A4 is the major enzyme involved in the metabolism of the substance P receptor antagonist aprepitant. Drug Metab Dispos 32:1287–1292.
  • Sandberg, M., Yasar, U., Stromberg, P., Hoog, J. O. Eliasson, E. (2002). Oxidation of celecoxib by polymorphic cytochrome P450 2C9 and alcohol dehydrogenase. Br J Clin Pharmacol 54:423–429.
  • Sanderink, G. J., Bournique, B., Stevens, J., Petry, M. Martinet, M. (1997). Involvement of human CYP1A isoenzymes in the metabolism and drug interactions of riluzole in vitro. J Pharmacol Exp Ther 282:1465–1472.
  • Sandwall, P., Lo, M. W., Jonzon, B., Dalen, P., Furtek, C., Ritter, M., Alvan, G., McCrea, J. Sjoqvist, F. (1999). Lack of polymorphism of the conversion of losartan to its active metabolite E-3174 in extensive and poor metabolizers of debrisoquine (cytochrome P450 2D6) and mephenytoin (cytochrome P450 2C19). Eur J Clin Pharmacol 55:279–283.
  • Sansen, S., Yano, J. K., Reynald, R. L., Schoch, G. A., Griffin, K. J., Stout, C. D. Johnson, E. F. (2007). Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J Biol Chem 282:14348–14355.
  • Sanwald, P., David, M. Dow, J. (1996a). Characterization of the cytochrome P450 enzymes involved in the in vitro metabolism of dolasetron. Comparison with other indole-containing 5-HT3 antagonists. Drug Metab Dispos 24:602–609.
  • Sanwald, P., David, M. Dow, J. (1996b). Use of electrospray ionization liquid chromatography-mass spectrometry to study the role of CYP2D6 in the in vitro metabolism of 5-hydroxytryptamine receptor antagonists. J Chromatogr B Biomed Appl 678:53–61.
  • Sapone, A., Vaira, D., Trespidi, S., Perna, F., Gatta, L., Tampieri, A., Ricci, C., Cantelli-Forti, G., Miglioli, M., Biagi, G. L. Paolini, M. (2003). The clinical role of cytochrome p450 genotypes in Helicobacter pylori management. Am J Gastroenterol 98:1010–1015.
  • Sarkar, M. A., Hunt, C., Guzelian, P. S. Karnes, H. T. (1992). Characterization of human liver cytochromes P-450 involved in theophylline metabolism. Drug Metab Dispos 20:31–37.
  • Sarkar, M. A. Jackson, B. J. (1994). Theophylline N-demethylations as probes for P4501A1 and P4501A2. Drug Metab Dispos 22:827–834.
  • Saruwatari, J., Matsunaga, M., Ikeda, K., Nakao, M., Oniki, K., Seo, T., Mihara, S., Marubayashi, T., Kamataki, T. Nakagawa, K. (2006). Impact of CYP2D6*10 on H1-antihistamine-induced hypersomnia. Eur J Clin Pharmacol 62:995–1001.
  • Sata, F., Sapone, A., Elizondo, G., Stocker, P., Miller, V. P., Zheng, W., Raunio, H., Crespi, C. L. Gonzalez, F. J. (2000). CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity. Clin Pharmacol Ther 67:48–56.
  • Savi, P., Combalbert, J., Gaich, C., Rouchon, M. C., Maffrand, J. P., Berger, Y. Herbert, J. M. (1994). The antiaggregating activity of clopidogrel is due to a metabolic activation by the hepatic cytochrome P450-1A. Thromb Haemost 72:313–317.
  • Savi, P. Herbert, J. M. (2005). Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Semin Thromb Hemost 31:174–183.
  • Savi, P., Pereillo, J. M., Uzabiaga, M. F., Combalbert, J., Picard, C., Maffrand, J. P., Pascal, M. Herbert, J. M. (2000). Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 84:891–896.
  • Saxena, R., Shaw, G. L., Relling, M. V., Frame, J. N., Moir, D. T., Evans, W. E., Caporaso, N. Weiffenbach, B. (1994). Identification of a new variant CYP2D6 allele with a single base deletion in exon 3 and its association with the poor metabolizer phenotype. Hum Mol Genet 3:923–926.
  • Schellens, J. H., van der Wart, J. H. Breimer, D. D. (1990). Relationship between mephenytoin oxidation polymorphism and phenytoin, methylphenytoin and phenobarbitone hydroxylation assessed in a phenotyped panel of healthy subjects. Br J Clin Pharmacol 29:665–671.
  • Schlicht, K. E., Michno, N., Smith, B. D., Scott, E. E. Murphy, S. E. (2007). Functional characterization of CYP2A13 polymorphisms. Xenobiotica 37:1439–1449.
  • Schmid, B., Bircher, J., Preisig, R. Kupfer, A. (1985). Polymorphic dextromethorphan metabolism: cosegregation of oxidative O-demethylation with debrisoquin hydroxylation. Clin Pharmacol Ther 38:618–624.
  • Schmidt, H., Vormfelde, S. V., Walchner-Bonjean, M., Klinder, K., Freudenthaler, S., Gleiter, C. H., Gundert-Remy, U., Skopp, G., Aderjan, R. Fuhr, U. (2003). The role of active metabolites in dihydrocodeine effects. Int J Clin Pharmacol Ther 41:95–106.
  • Schoch, G. A., Yano, J. K., Wester, M. R., Griffin, K. J., Stout, C. D. Johnson, E. F. (2004). Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J Biol Chem 279:9497–9503.
  • Schoedel, K. A., Hoffmann, E. B., Rao, Y., Sellers, E. M. Tyndale, R. F. (2004). Ethnic variation in CYP2A6 and association of genetically slow nicotine metabolism and smoking in adult Caucasians. Pharmacogenetics 14:615–626.
  • Schotte, A., Janssen, P. F., Gommeren, W., Luyten, W. H., Van Gompel, P., Lesage, A. S., De Loore, K., Leysen, J. E. (1996). Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl) 124:57–73.
  • Schrader, B. J. Bauman, J. L. (1986). Mexiletine: a new type I antiarrhythmic agent. Drug Intell Clin Pharm 20:255–260.
  • Schroeder, D. H. (1983). Metabolism and kinetics of bupropion. J Clin Psychiatry 44:79–81.
  • Schroth, W., Antoniadou, L., Fritz, P., Schwab, M., Muerdter, T., Zanger, U. M., Simon, W., Eichelbaum, M. Brauch, H. (2007). Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol 25:5187–5193.
  • Schuetz, J. D. Guzelian, P. S. (1995). Isolation of CYP3A5P cDNA from human liver: a reflection of a novel cytochrome P-450 pseudogene. Biochim Biophys Acta 1261:161–165.
  • Schulz-Utermoehl, T., Bennett, A. J., Ellis, S. W., Tucker, G. T., Boobis, A. R. Edwards, R. J. (1999). Polymorphic debrisoquine 4-hydroxylase activity in the rat is due to differences in CYP2D2 expression. Pharmacogenetics 9:357–366.
  • Schwab, M., Klotz, U., Hofmann, U., Schaeffeler, E., Leodolter, A., Malfertheiner, P. Treiber, G. (2005). Esomeprazole-induced healing of gastroesophageal reflux disease is unrelated to the genotype of CYP2C19: evidence from clinical and pharmacokinetic data. Clin Pharmacol Ther 78:627–634.
  • Schwabe, U., Ukena, D. Lohse, M. J. (1985). Xanthine derivatives as antagonists at A1 and A2 adenosine receptors. Naunyn Schmiedebergs Arch Pharmacol 330:212–221.
  • Schwartzberg, L. S. (2007). Chemotherapy-induced nausea and vomiting: which antiemetic for which therapy? Oncology (Williston Park) 21:946–953; discussion, 954, 959, 962 passim.
  • Schwarz, D., Kisselev, P., Cascorbi, I., Schunck, W. H. Roots, I. (2001). Differential metabolism of benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol by human CYP1A1 variants. Carcinogenesis 22:453–459.
  • Schwarz, D., Kisselev, P., Schunck, W. H., Chernogolov, A., Boidol, W., Cascorbi, I. Roots, I. (2000). Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity. Pharmacogenetics 10:519–530.
  • Schweikl, H., Taylor, J. A., Kitareewan, S., Linko, P., Nagorney, D. Goldstein, J. A. (1993). Expression of CYP1A1 and CYP1A2 genes in human liver. Pharmacogenetics 3:239–249.
  • Scordo, M. G., Aklillu, E., Yasar, U., Dahl, M. L., Spina, E. Ingelman-Sundberg, M. (2001). Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population. Br J Clin Pharmacol 52:447–450.
  • Scordo, M. G., Dahl, M. L., Spina, E., Cordici, F. Arena, M. G. (2006). No association between CYP2D6 polymorphism and Alzheimer’s disease in an Italian population. Pharmacol Res 53:162–165.
  • Scordo, M. G., Spina, E., Dahl, M. L., Gatti, G. Perucca, E. (2005). Influence of CYP2C9, 2C19, and 2D6 genetic polymorphisms on the steady-state plasma concentrations of the enantiomers of fluoxetine and norfluoxetine. Basic Clin Pharmacol Toxicol 97:296–301.
  • Scordo, M. G., Spina, E., Facciola, G., Avenoso, A., Johansson, I. Dahl, M. L. (1999). Cytochrome P450 2D6 genotype and steady-state plasma levels of risperidone and 9-hydroxyrisperidone. Psychopharmacology (Berl) 147:300–305.
  • Scripture, C. D. Pieper, J. A. (2001). Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet 40:263–281.
  • Segura, M., Farre, M., Pichini, S., Peiro, A. M., Roset, P. N., Ramirez, A., Ortuno, J., Pacifici, R., Zuccaro, P., Segura, J. de la Torre, R. (2005). Contribution of cytochrome P450 2D6 to 3,4-methylenedioxymethamphetamine disposition in humans: use of paroxetine as a metabolic inhibitor probe. Clin Pharmacokinet 44:649–660.
  • Sekino, K., Kubota, T., Okada, Y., Yamada, Y., Yamamoto, K., Horiuchi, R., Kimura, K. Iga, T. (2003). Effect of the single CYP2C9*3 allele on pharmacokinetics and pharmacodynamics of losartan in healthy Japanese subjects. Eur J Clin Pharmacol 59:589–592.
  • Sellers, E. M., Kaplan, H. L. Tyndale, R. F. (2000). Inhibition of cytochrome P450 2A6 increases nicotine’s oral bioavailability and decreases smoking. Clin Pharmacol Ther 68:35–43.
  • Sellers, T. A., Schildkraut, J. M., Pankratz, V. S., Vierkant, R. A., Fredericksen, Z. S., Olson, J. E., Cunningham, J., Taylor, W., Liebow, M., McPherson, C., Hartmann, L. C., Pal, T. Adjei, A. A. (2005). Estrogen bioactivation, genetic polymorphisms, and ovarian cancer. Cancer Epidemiol Biomarkers Prev 14:2536–2543.
  • Seltzer, B. (2005). Donepezil: a review. Expert Opin Drug Metab Toxicol 1:527–536.
  • Seltzer, B. (2007). Donepezil: an update. Expert Opin Pharmacother 8:1011–1023.
  • Senda, C., Yamaura, Y., Kobayashi, K., Fujii, H., Minami, H., Sasaki, Y., Igarashi, T. Chiba, K. (2001). Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes. Br J Clin Pharmacol 52:100–103.
  • Sengstag, C., Eugster, H. P. Wurgler, F. E. (1994). High promutagen activating capacity of yeast microsomes containing human cytochrome P-450 1A and human NADPH-cytochrome P-450 reductase. Carcinogenesis 15:837–843.
  • Seo, T., Nagata, R., Ishitsu, T., Murata, T., Takaishi, C., Hori, M. Nakagawa, K. (2008). Impact of CYP2C19 polymorphisms on the efficacy of clobazam therapy. Pharmacogenomics 9:527–537.
  • Shahidi, N. T. (1967). Acetophenetidin sensitivity. Am J Dis Child 113:81–82.
  • Shams, M. E., Arneth, B., Hiemke, C., Dragicevic, A., Muller, M. J., Kaiser, R., Lackner, K. Hartter, S. (2006). CYP2D6 polymorphism and clinical effect of the antidepressant venlafaxine. J Clin Pharm Ther 31:493–502.
  • Shang, Y. (2006). Molecular mechanisms of oestrogen and SERMs in endometrial carcinogenesis. Nat Rev Cancer 6:360–368.
  • Sharma, A. Hamelin, B. A. (2003). Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird’s eye view. Curr Drug Metab 4:105–129.
  • Sharma, S. (2007). Antiarrhythmic drugs: present and future. J Assoc Physicians India 55(Suppl):43–46.
  • Shelly, W., Draper, M. W., Krishnan, V., Wong, M. Jaffe, R. B. (2008). Selective estrogen receptor modulators: an update on recent clinical findings. Obstet Gynecol Surv 63:163–181.
  • Shen, H., He, M. M., Liu, H., Wrighton, S. A., Wang, L., Guo, B. Li, C. (2007). Comparative metabolic capabilities and inhibitory profiles of CYP2D6.1, CYP2D6.10, and CYP2D6.17. Drug Metab Dispos 35:1292–1300.
  • Shen, S., Marchick, M. R., Davis, M. R., Doss, G. A. Pohl, L. R. (1999). Metabolic activation of diclofenac by human cytochrome P450 3A4: role of 5-hydroxydiclofenac. Chem Res Toxicol 12:214–222.
  • Sheng, J., Guo, J., Hua, Z., Caggana, M. Ding, X. (2000). Characterization of human CYP2G genes: widespread loss-of-function mutations and genetic polymorphism. Pharmacogenetics 10:667–678.
  • Shet, M. S., McPhaul, M., Fisher, C. W., Stallings, N. R. Estabrook, R. W. (1997). Metabolism of the antiandrogenic drug (Flutamide) by human CYP1A2. Drug Metab Dispos 25:1298–1303.
  • Shi, X., Zhou, S., Wang, Z., Zhou, Z. Wang, Z. (2008). CYP1A1 and GSTM1 polymorphisms and lung cancer risk in Chinese populations: a meta-analysis. Lung Cancer 59:155–163.
  • Shibutani, S., Dasaradhi, L., Terashima, I., Banoglu, E. Duffel, M. W. (1998a). Alpha-hydroxytamoxifen is a substrate of hydroxysteroid (alcohol) sulfotransferase, resulting in tamoxifen DNA adducts. Cancer Res 58:647–653.
  • Shibutani, S., Shaw, P. M., Suzuki, N., Dasaradhi, L., Duffel, M. W. Terashima, I. (1998b). Sulfation of alpha-hydroxytamoxifen catalyzed by human hydroxysteroid sulfotransferase results in tamoxifen-DNA adducts. Carcinogenesis 19:2007–2011.
  • Shigeta, M. Homma, A. (2001). Donepezil for Alzheimer’s disease: pharmacodynamic, pharmacokinetic, and clinical profiles. CNS Drug Rev 7:353–368.
  • Shih, P. S. Huang, J. D. (2002). Pharmacokinetics of midazolam and 1’-hydroxymidazolam in Chinese with different CYP3A5 genotypes. Drug Metab Dispos 30:1491–1496.
  • Shimada, T., Gillam, E. M., Oda, Y., Tsumura, F., Sutter, T. R., Guengerich, F. P. Inoue, K. (1999). Metabolism of benzo[a]pyrene to trans-7,8-dihydroxy-7, 8-dihydrobenzo[a]pyrene by recombinant human cytochrome P450 1B1 and purified liver epoxide hydrolase. Chem Res Toxicol 12:623–629.
  • Shimada, T., Hayes, C. L., Yamazaki, H., Amin, S., Hecht, S. S., Guengerich, F. P. Sutter, T. R. (1996a). Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1. Cancer Res 56:2979–2984.
  • Shimada, T., Tsumura, F., Yamazaki, H., Guengerich, F. P. Inoue, K. (2001). Characterization of (+/-)-bufuralol hydroxylation activities in liver microsomes of Japanese and Caucasian subjects genotyped for CYP2D6. Pharmacogenetics 11:143–156.
  • Shimada, T., Yamazaki, H. Guengerich, F. P. (1996b). Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations. Xenobiotica 26:395–403.
  • Shimada, T., Yamazaki, H., Mimura, M., Inui, Y. Guengerich, F. P. (1994). Interindividual variations in human liver cytochrome P450 enzymes involved in the oxidation of drugs, carcinogens, and toxic chemicals. J Pharmacol Exp Ther 270:414–423.
  • Shimada, T., Yamazaki, H., Mimura, M., Wakamiya, N., Ueng, Y. F., Guengerich, F. P. Inui, Y. (1996c). Characterization of microsomal cytochrome P450 enzymes involved in the oxidation of xenobiotic chemicals in human fetal liver and adult lungs. Drug Metab Dispos 24:515–522.
  • Shimamoto, J., Ieiri, I., Urae, A., Kimura, M., Irie, S., Kubota, T., Chiba, K., Ishizaki, T., Otsubo, K. Higuchi, S. (2000). Lack of differences in diclofenac (a substrate for CYP2C9) pharmacokinetics in healthy volunteers with respect to the single CYP2C9*3 allele. Eur J Clin Pharmacol 56:65–68.
  • Shimizu, M., Takatori, K., Kajiwara, M. Ogata, H. (1998). Isolation of a major metabolite (i-OHAP) of aprindine and its identification as N-[3-(N,N-diethylamino)propyl]-N-phenyl-2-aminoindan- 5-ol. Biol Pharm Bull 21:530–534.
  • Shimoda, K., Morita, S., Hirokane, G., Yokono, A., Someya, T. Takahashi, S. (2000a). Metabolism of desipramine in Japanese psychiatric patients: the impact of CYP2D6 genotype on the hydroxylation of desipramine. Pharmacol Toxicol 86:245–249.
  • Shimoda, K., Morita, S., Yokono, A., Someya, T., Hirokane, G., Sunahara, N. Takahashi, S. (2000b). CYP2D6*10 alleles are not the determinant of the plasma haloperidol concentrations in Asian patients. Ther Drug Monit 22:392–396.
  • Shimoda, K., Someya, T., Morita, S., Hirokane, G., Yokono, A., Takahashi, S. Okawa, M. (2002a). Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position −2964 in the 5’-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 26:261–265.
  • Shimoda, K., Someya, T., Yokono, A., Morita, S., Hirokane, G., Takahashi, S. Okawa, M. (2002b). The impact of CYP2C19 and CYP2D6 genotypes on metabolism of amitriptyline in Japanese psychiatric patients. J Clin Psychopharmacol 22:371–378.
  • Shintani, M., Ieiri, I., Inoue, K., Mamiya, K., Ninomiya, H., Tashiro, N., Higuchi, S. Otsubo, K. (2001). Genetic polymorphisms and functional characterization of the 5’-flanking region of the human CYP2C9 gene: in vitro and in vivo studies. Clin Pharmacol Ther 70:175–182.
  • Shiraga, T., Kaneko, H., Iwasaki, K., Tozuka, Z., Suzuki, A. Hata, T. (1999). Identification of cytochrome P450 enzymes involved in the metabolism of zotepine, an antipsychotic drug, in human liver microsomes. Xenobiotica 29:217–229.
  • Shirai, N., Furuta, T., Moriyama, Y., Okochi, H., Kobayashi, K., Takashima, M., Xiao, F., Kosuge, K., Nakagawa, K., Hanai, H., Chiba, K., Ohashi, K. Ishizaki, T. (2001). Effects of CYP2C19 genotypic differences in the metabolism of omeprazole and rabeprazole on intragastric pH. Aliment Pharmacol Ther 15:1929–1937.
  • Shirai, N., Furuta, T., Xiao, F., Kajimura, M., Hanai, H., Ohashi, K. Ishizaki, T. (2002). Comparison of lansoprazole and famotidine for gastric acid inhibition during the daytime and night-time in different CYP2C19 genotype groups. Aliment Pharmacol Ther 16:837–846.
  • Shiraishi, T., Hosokawa, M., Kobayashi, K., Tainaka, H., Yamaura, Y., Taguchi, M. Chiba, K. (2002). Effects of G169R and P34S substitutions produced by mutations of CYP2D6*14 on the functional properties of CYP2D6 expressed in V79 cells. Drug Metab Dispos 30:1201–1205.
  • Shitara, Y., Horie, T. Sugiyama, Y. (2006). Transporters as a determinant of drug clearance and tissue distribution. Eur J Pharm Sci 27:425–446.
  • Shon, J. H., Yoon, Y. R., Kim, K. A., Lim, Y. C., Lee, K. J., Park, J. Y., Cha, I. J., Flockhart, D. A. Shin, J. G. (2002). Effects of CYP2C19 and CYP2C9 genetic polymorphisms on the disposition of and blood glucose lowering response to tolbutamide in humans. Pharmacogenetics 12:111–119.
  • Si, D., Guo, Y., Zhang, Y., Yang, L., Zhou, H. Zhong, D. (2004). Identification of a novel variant CYP2C9 allele in Chinese. Pharmacogenetics 14:465–469.
  • Siddoway, L. A., Roden, D. M. Woosley, R. L. (1984). Clinical pharmacology of propafenone: pharmacokinetics, metabolism, and concentration-response relations. Am J Cardiol 54:9D–12D.
  • Siddoway, L. A., Thompson, K. A., McAllister, C. B., Wang, T., Wilkinson, G. R., Roden, D. M. Woosley, R. L. (1987). Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation 75:785–791.
  • Siegle, I., Fritz, P., Eckhardt, K., Zanger, U. M. Eichelbaum, M. (2001). Cellular localization and regional distribution of CYP2D6 mRNA and protein expression in human brain. Pharmacogenetics 11:237–245.
  • Silig, Y., Pinarbasi, H., Gunes, S., Ayan, S., Bagci, H. Cetinkaya, O. (2006). Polymorphisms of CYP1A1, GSTM1, GSTT1, and prostate cancer risk in Turkish population. Cancer Invest 24:41–45.
  • Silverman, E., Mouy, R., Spiegel, L., Jung, L. K., Saurenmann, R. K., Lahdenne, P., Horneff, G., Calvo, I., Szer, I. S., Simpson, K., Stewart, J. A. Strand, V. (2005). Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med 352:1655–1666.
  • Sim, S. C., Risinger, C., Dahl, M. L., Aklillu, E., Christensen, M., Bertilsson, L. Ingelman-Sundberg, M. (2006). A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants. Clin Pharmacol Ther 79:103–113.
  • Simons, P. J., Cockshott, I. D., Douglas, E. J., Gordon, E. A., Hopkins, K. Rowland, M. (1988). Disposition in male volunteers of a subanaesthetic intravenous dose of an oil in water emulsion of 14C-propofol. Xenobiotica 18:429–440.
  • Simpson, K., Spencer, C. M. McClellan, K. J. (2000). Tropisetron: an update of its use in the prevention of chemotherapy-induced nausea and vomiting. Drugs 59:1297–1315.
  • Sinclair, P. R., Gorman, N., Dalton, T., Walton, H. S., Bement, W. J., Sinclair, J. F., Smith, A. G. Nebert, D. W. (1998a). Uroporphyria produced in mice by iron and 5-aminolaevulinic acid does not occur in Cyp1a2(-/-) null mutant mice. Biochem J 330 (Pt 1):149–153.
  • Sinclair, P. R., Gorman, N., Tsyrlov, I. B., Fuhr, U., Walton, H. S. Sinclair, J. F. (1998b). Uroporphyrinogen oxidation catalyzed by human cytochromes P450. Drug Metab Dispos 26:1019–1025.
  • Sinclair, P. R., Gorman, N., Walton, H. S., Bement, W. J., Dalton, T. P., Sinclair, J. F., Smith, A. G. Nebert, D. W. (2000). CYP1A2 is essential in murine uroporphyria caused by hexachlorobenzene and iron. Toxicol Appl Pharmacol 162:60–67.
  • Sinclair, P. R., Gorman, N., Walton, H. S., Sinclair, J. F., Lee, C. A. Rifkind, A. B. (1997). Identification of CYP1A5 as the CYP1A enzyme mainly responsible for uroporphyrinogen oxidation induced by AH receptor ligands in chicken liver and kidney. Drug Metab Dispos 25:779–783.
  • Sindrup, S. H., Brosen, K. Gram, L. F. (1992a). Pharmacokinetics of the selective serotonin reuptake inhibitor paroxetine: nonlinearity and relation to the sparteine oxidation polymorphism. Clin Pharmacol Ther 51:288–295.
  • Sindrup, S. H., Brosen, K., Gram, L. F., Hallas, J., Skjelbo, E., Allen, A., Allen, G. D., Cooper, S. M., Mellows, G., Tasker, T. C. et al. (1992b). The relationship between paroxetine and the sparteine oxidation polymorphism. Clin Pharmacol Ther 51:278–287.
  • Sindrup, S. H., Brosen, K., Hansen, M. G., Aaes-Jorgensen, T., Overo, K. F. Gram, L. F. (1993). Pharmacokinetics of citalopram in relation to the sparteine and the mephenytoin oxidation polymorphisms. Ther Drug Monit 15:11–17.
  • Sindrup, S. H., Gram, L. F., Skjold, T., Grodum, E., Brosen, K. Beck-Nielsen, H. (1990). Clomipramine vs desipramine vs placebo in the treatment of diabetic neuropathy symptoms. A double-blind, cross-over study. Br J Clin Pharmacol 30:683–691.
  • Sindrup, S. H., Tuxen, C., Gram, L. F., Grodum, E., Skjold, T., Brosen, K. Beck-Nielsen, H. (1992c). Lack of effect of mianserin on the symptoms of diabetic neuropathy. Eur J Clin Pharmacol 43:251–255.
  • Singer, C., Tractenberg, R. E., Kaye, J., Schafer, K., Gamst, A., Grundman, M., Thomas, R. Thal, L. J. (2003). A multicenter, placebo-controlled trial of melatonin for sleep disturbance in Alzheimer’s disease. Sleep 26:893–901.
  • Singh, B. N. (2006). Amiodarone: a multifaceted antiarrhythmic drug. Curr Cardiol Rep 8:349–355.
  • Singh, G., Saxena, N., Aggarwal, A. Misra, R. (2007). Cytochrome p450 polymorphism as a predictor of ovarian toxicity to pulse cyclophosphamide in systemic lupus erythematosus. J Rheumatol 34:731–733.
  • Skene, D. J., Papagiannidou, E., Hashemi, E., Snelling, J., Lewis, D. F., Fernandez, M. Ioannides, C. (2001). Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices. J Pineal Res 31:333–342.
  • Skjelbo, E., Brosen, K., Hallas, J. Gram, L. F. (1991). The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine. Clin Pharmacol Ther 49:18–23.
  • Skoda, R. C., Gonzalez, F. J., Demierre, A. Meyer, U. A. (1988). Two mutant alleles of the human cytochrome P-450db1 gene (P450C2D1) associated with genetically deficient metabolism of debrisoquine and other drugs. Proc Natl Acad Sci U S A 85:5240–5243.
  • Skowron, G. (1998). dNN study: stavudine, nelfinavir and nevirapine. Preliminary safety, activity, and pharmacokinetic interactions. Antivir Ther 3(Suppl 4):61–62.
  • Skurnik, Y. D., Tcherniak, A., Edlan, K. Sthoeger, Z. (2003). Ticlopidine-induced cholestatic hepatitis. Ann Pharmacother 37:371–375.
  • Slanar, O., Nobilis, M., Kvetina, J., Mikoviny, R., Zima, T., Idle, J. R. Perlik, F. (2007). Miotic action of tramadol is determined by CYP2D6 genotype. Physiol Res 56:129–136.
  • Smart, J. Daly, A. K. (2000). Variation in induced CYP1A1 levels: relationship to CYP1A1, Ah receptor, and GSTM1 polymorphisms. Pharmacogenetics 10:11–24.
  • Smith, A. G., Clothier, B., Carthew, P., Childs, N. L., Sinclair, P. R., Nebert, D. W. Dalton, T. P. (2001). Protection of the Cyp1a2(-/-) null mouse against uroporphyria and hepatic injury following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Appl Pharmacol 173:89–98.
  • Smith, G. B., Bend, J. R., Bedard, L. L., Reid, K. R., Petsikas, D. Massey, T. E. (2003). Biotransformation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in peripheral human lung microsomes. Drug Metab Dispos 31:1134–1141.
  • Smith, G. H. (1985). Flecainide: a new class Ic antidysrhythmic. Drug Intell Clin Pharm 19:703–707.
  • Sneyd, J. R., Simons, P. J. Wright, B. (1994). Use of proton nmr spectroscopy to measure propofol metabolites in the urine of the female Caucasian patient. Xenobiotica 24:1021–1028.
  • Soga, Y., Nishimura, F., Ohtsuka, Y., Araki, H., Iwamoto, Y., Naruishi, H., Shiomi, N., Kobayashi, Y., Takashiba, S., Shimizu, K., Gomita, Y. Oka, E. (2004). CYP2C polymorphisms, phenytoin metabolism, and gingival overgrowth in epileptic subjects. Life Sci 74:827–834.
  • Sohn, D. R., Kusaka, M., Ishizaki, T., Shin, S. G., Jang, I. J., Shin, J. G. Chiba, K. (1992). Incidence of S-mephenytoin hydroxylation deficiency in a Korean population and the interphenotypic differences in diazepam pharmacokinetics. Clin Pharmacol Ther 52:160–169.
  • Soininen, K., Kleimola, T., Elomaa, I., Salmo, M. Rissanen, P. (1986). The steady-state pharmacokinetics of tamoxifen and its metabolites in breast cancer patients. J Int Med Res 14:162–165.
  • Solas, C., Poizot-Martin, I., Drogoul, M. P., Ravaux, I., Dhiver, C., Lafeuillade, A., Allegre, T., Mokhtari, M., Moreau, J., Lepeu, G., Petit, N., Durand, A. Lacarelle, B. (2004). Therapeutic drug monitoring of lopinavir/ritonavir given alone or with a non-nucleoside reverse transcriptase inhibitor. Br J Clin Pharmacol 57:436–440.
  • Solus, J. F., Arietta, B. J., Harris, J. R., Sexton, D. P., Steward, J. Q., McMunn, C., Ihrie, P., Mehall, J. M., Edwards, T. L. Dawson, E. P. (2004). Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics 5:895–931.
  • Somani, P. (1980). Antiarrhythmic effects of flecainide. Clin Pharmacol Ther 27:464–470.
  • Somogyi, A. A., Barratt, D. T. Coller, J. K. (2007). Pharmacogenetics of opioids. Clin Pharmacol Ther 81:429–444.
  • Sotaniemi, E. A., Rautio, A., Backstrom, M., Arvela, P. Pelkonen, O. (1995). CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in patients with liver and kidney diseases and epileptic patients. Br J Clin Pharmacol 39:71–76.
  • Soucek, P. (1999). Expression of cytochrome P450 2A6 in Escherichia coli: purification, spectral, and catalytic characterization, and preparation of polyclonal antibodies. Arch Biochem Biophys 370:190–200.
  • Soyama, A., Hanioka, N., Saito, Y., Murayama, N., Ando, M., Ozawa, S. Sawada, J. (2002a). Amiodarone N-deethylation by CYP2C8 and its variants, CYP2C8*3 and CYP2C8 P404A. Pharmacol Toxicol 91:174–178.
  • Soyama, A., Kubo, T., Miyajima, A., Saito, Y., Shiseki, K., Komamura, K., Ueno, K., Kamakura, S., Kitakaze, M., Tomoike, H., Ozawa, S. Sawada, J. (2004). Novel nonsynonymous single-nucleotide polymorphisms in the CYP2D6 gene. Drug Metab Pharmacokinet 19:313–319.
  • Soyama, A., Saito, Y., Hanioka, N., Maekawa, K., Komamura, K., Kamakura, S., Kitakaze, M., Tomoike, H., Ueno, K., Goto, Y., Kimura, H., Katoh, M., Sugai, K., Saitoh, O., Kawai, M., Ohnuma, T., Ohtsuki, T., Suzuki, C., Minami, N., Kamatani, N., Ozawa, S. Sawada, J. (2005). Single-nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population. Drug Metab Pharmacokinet 20:24–33.
  • Soyama, A., Saito, Y., Hanioka, N., Murayama, N., Nakajima, O., Katori, N., Ishida, S., Sai, K., Ozawa, S. Sawada, J. I. (2001). Nonsynonymous single nucleotide alterations found in the CYP2C8 gene result in reduced in vitro paclitaxel metabolism. Biol Pharm Bull 24:1427–1430.
  • Soyama, A., Saito, Y., Komamura, K., Ueno, K., Kamakura, S., Ozawa, S. Sawada, J. (2002b). Five novel single-nucleotide polymorphisms in the CYP2C8 gene, one of which induces a frame-shift. Drug Metab Pharmacokinet 17:374–377.
  • Soyama, A., Saito, Y., Kubo, T., Miyajima, A., Ohno, Y., Komamura, K., Ueno, K., Kamakura, S., Kitakaze, M., Tomoike, H., Ozawa, S. Sawada, J. (2006). Sequence-based analysis of the CYP2D6*36-CYP2D6*10 tandem-type arrangement, a major CYP2D6*10 haplotype in the Japanese population. Drug Metab Pharmacokinet 21:208–216.
  • Spaldin, V., Madden, S., Adams, D. A., Edwards, R. J., Davies, D. S. Park, B. K. (1995). Determination of human hepatic cytochrome P4501A2 activity in vitro use of tacrine as an isoenzyme-specific probe. Drug Metab Dispos 23:929–934.
  • Spaldin, V., Madden, S., Pool, W. F., Woolf, T. F. Park, B. K. (1994). The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes. Br J Clin Pharmacol 38:15–22.
  • Spigset, O., Axelsson, S., Norstrom, A., Hagg, S. Dahlqvist, R. (2001). The major fluvoxamine metabolite in urine is formed by CYP2D6. Eur J Clin Pharmacol 57:653–658.
  • Spigset, O., Granberg, K., Hagg, S., Soderstrom, E. Dahlqvist, R. (1998). Nonlinear fluvoxamine disposition. Br J Clin Pharmacol 45:257–263.
  • Spina, E., Avenoso, A., Facciola, G., Salemi, M., Scordo, M. G., Giacobello, T., Madia, A. G. Perucca, E. (2000). Plasma concentrations of risperidone and 9-hydroxyrisperidone: effect of comedication with carbamazepine or valproate. Ther Drug Monit 22:481–485.
  • Spina, E., Gitto, C., Avenoso, A., Campo, G. M., Caputi, A. P. Perucca, E. (1997). Relationship between plasma desipramine levels, CYP2D6 phenotype and clinical response to desipramine: a prospective study. Eur J Clin Pharmacol 51:395–398.
  • Spina, E., Steiner, E., Ericsson, O. Sjoqvist, F. (1987). Hydroxylation of desmethylimipramine: dependence on the debrisoquin hydroxylation phenotype. Clin Pharmacol Ther 41:314–319.
  • Spink, D. C., Eugster, H. P., Lincoln, D. W., 2nd, Schuetz, J. D., Schuetz, E. G., Johnson, J. A., Kaminsky, L. S. Gierthy, J. F. (1992). 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA. Arch Biochem Biophys 293:342–348.
  • Spink, D. C., Hayes, C. L., Young, N. R., Christou, M., Sutter, T. R., Jefcoate, C. R. Gierthy, J. F. (1994). The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on estrogen metabolism in MCF-7 breast cancer cells: evidence for induction of a novel 17 beta-estradiol 4-hydroxylase. J Steroid Biochem Mol Biol 51:251–258.
  • Spracklin, D. K., Thummel, K. E. Kharasch, E. D. (1996). Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4. Drug Metab Dispos 24:976–983.
  • Spurdle, A. B., Goodwin, B., Hodgson, E., Hopper, J. L., Chen, X., Purdie, D. M., McCredie, M. R., Giles, G. G., Chenevix-Trench, G. Liddle, C. (2002). The CYP3A4*1B polymorphism has no functional significance and is not associated with risk of breast or ovarian cancer. Pharmacogenetics 12:355–366.
  • Spurr, N. K., Gough, A. C., Stevenson, K. Wolf, C. R. (1987). Msp-1 polymorphism detected with a cDNA probe for the P-450 I family on chromosome 15. Nucleic Acids Res 15:5901.
  • Spurr, N. K., Gough, A. C., Stevenson, K. Wolf, C. R. (1989). The human cytochrome P450 CYP3A locus: assignment to chromosome 7q22-qter. Hum Genet 81:171–174.
  • Srivastava, P. K., Yun, C. H., Beaune, P. H., Ged, C. Guengerich, F. P. (1991). Separation of human liver microsomal tolbutamide hydroxylase and (S)-mephenytoin 4’-hydroxylase cytochrome P-450 enzymes. Mol Pharmacol 40:69–79.
  • Stamer, U. M., Lehnen, K., Hothker, F., Bayerer, B., Wolf, S., Hoeft, A. Stuber, F. (2003). Impact of CYP2D6 genotype on postoperative tramadol analgesia. Pain 105:231–238.
  • Stearns, R. A., Chakravarty, P. K., Chen, R. Chiu, S. H. (1995). Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members. Drug Metab Dispos 23:207–215.
  • Stearns, R. A., Miller, R. R., Doss, G. A., Chakravarty, P. K., Rosegay, A., Gatto, G. J. Chiu, S. H. (1992). The metabolism of DuP 753, a nonpeptide angiotensin II receptor antagonist, by rat, monkey, and human liver slices. Drug Metab Dispos 20:281–287.
  • Stearns, V., Johnson, M. D., Rae, J. M., Morocho, A., Novielli, A., Bhargava, P., Hayes, D. F., Desta, Z. Flockhart, D. A. (2003). Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor, paroxetine. J Natl Cancer Inst 95:1758–1764.
  • Stedman, C. A., Begg, E. J., Kennedy, M. A., Roberts, R. Wilkinson, T. J. (2002). Cytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemia. Hum Psychopharmacol 17:187–190.
  • Steen, V. M., Andreassen, O. A., Daly, A. K., Tefre, T., Borresen, A. L., Idle, J. R. Gulbrandsen, A. K. (1995a). Detection of the poor metabolizer-associated CYP2D6(D) gene deletion allele by long-PCR technology. Pharmacogenetics 5:215–223.
  • Steen, V. M., Molven, A., Aarskog, N. K. Gulbrandsen, A. K. (1995b). Homologous unequal cross-over involving a 2.8-kb direct repeat as a mechanism for the generation of allelic variants of human cytochrome P450 CYP2D6 gene. Hum Mol Genet 4:2251–2257.
  • Steimer, W., Zopf, K., von Amelunxen, S., Pfeiffer, H., Bachofer, J., Popp, J., Messner, B., Kissling, W., Leucht, S. (2004). Allele-specific change of concentration and functional gene dose for the prediction of steady-state serum concentrations of amitriptyline and nortriptyline in CYP2C19 and CYP2D6 extensive and intermediate metabolizers. Clin Chem 50:1623–1633.
  • Steimer, W., Zopf, K., von Amelunxen, S., Pfeiffer, H., Bachofer, J., Popp, J., Messner, B., Kissling, W., Leucht, S. (2005). Amitriptyline or not, that is the question: pharmacogenetic testing of CYP2D6 and CYP2C19 identifies patients with low or high risk for side effects in amitriptyline therapy. Clin Chem 51:376–385.
  • Steiner, E. Spina, E. (1987). Differences in the inhibitory effect of cimetidine on desipramine metabolism between rapid and slow debrisoquin hydroxylators. Clin Pharmacol Ther 42:278–282.
  • Stempak, D., Bukaveckas, B. L., Linder, M., Koren, G. Baruchel, S. (2005). Cytochrome P450 2C9 genotype: impact on celecoxib safety and pharmacokinetics in a pediatric patient. Clin Pharmacol Ther 78:309–310.
  • Stocker, H., Kruse, G., Kreckel, P., Herzmann, C., Arasteh, K., Claus, J., Jessen, H., Cordes, C., Hintsche, B., Schlote, F., Schneider, L. Kurowski, M. (2004). Nevirapine significantly reduces the levels of racemic methadone and (R)-methadone in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 48:4148–4153.
  • Stollberger, C., Huber, J. O. Finsterer, J. (2005). Antipsychotic drugs and QT prolongation. Int Clin Psychopharmacol 20:243–251.
  • Stormer, E., von Moltke, L. L., Shader, R. I. Greenblatt, D. J. (2000). Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P-450 1A2, 2D6, and 3A4. Drug Metab Dispos 28:1168–1175.
  • Stoschitzky, K., Klein, W., Stark, G., Stark, U., Zernig, G., Graziadei, I. Lindner, W. (1990). Different stereoselective effects of (R)- and (S)-propafenone: clinical pharmacologic, electrophysiologic, and radioligand binding studies. Clin Pharmacol Ther 47:740–746.
  • Stresser, D. M. Kupfer, D. (1998). Human cytochrome P450-catalyzed conversion of the proestrogenic pesticide methoxychlor into an estrogen. Role of CYP2C19 and CYP1A2 in O-demethylation. Drug Metab Dispos 26:868–874.
  • Stresser, D. M. Kupfer, D. (1999). Monospecific antipeptide antibody to cytochrome P-450 2B6. Drug Metab Dispos 27:517–525.
  • Stucker, I., Jacquet, M., de Waziers, I., Cenee, S., Beaune, P., Kremers, P., Hemon, D. (2000). Relation between inducibility of CYP1A1, GSTM1, and lung cancer in a French population. Pharmacogenetics 10:617–627.
  • Su, T., Bao, Z., Zhang, Q. Y., Smith, T. J., Hong, J. Y. Ding, X. (2000). Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high-efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Cancer Res 60:5074–5079.
  • Su, T., Sheng, J. J., Lipinskas, T. W. Ding, X. (1996). Expression of CYP2A genes in rodent and human nasal mucosa. Drug Metab Dispos 24:884–890.
  • Subrahmanyam, V., Renwick, A. B., Walters, D. G., Young, P. J., Price, R. J., Tonelli, A. P. Lake, B. G. (2001). Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos 29:1146–1155.
  • Sugawara, T., Nomura, E., Sagawa, T., Sakuragi, N. Fujimoto, S. (2003). CYP1A1 polymorphism and risk of gynecological malignancy in Japan. Int J Gynecol Cancer 13:785–790.
  • Sugidachi, A., Asai, F., Ogawa, T., Inoue, T. Koike, H. (2000). The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol 129:1439–1446.
  • Sugidachi, A., Asai, F., Yoneda, K., Iwamura, R., Ogawa, T., Otsuguro, K. Koike, H. (2001). Antiplatelet action of R-99224, an active metabolite of a novel thienopyridine-type G(i)-linked P2T antagonist, CS-747. Br J Pharmacol 132:47–54.
  • Sugimoto, H., Yamanishi, Y., Iimura, Y. Kawakami, Y. (2000). Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors. Curr Med Chem 7:303–339.
  • Sullivan-Klose, T. H., Ghanayem, B. I., Bell, D. A., Zhang, Z. Y., Kaminsky, L. S., Shenfield, G. M., Miners, J. O., Birkett, D. J. Goldstein, J. A. (1996). The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 6:341–349.
  • Sullivan, H. R. Due, S. L. (1973). Urinary metabolites of dl-methadone in maintenance subjects. J Med Chem 16:909–913.
  • Sun, D., Chen, G., Dellinger, R. W., Duncan, K., Fang, J. L. Lazarus, P. (2006). Characterization of tamoxifen and 4-hydroxytamoxifen glucuronidation by human UGT1A4 variants. Breast Cancer Res 8:R50.
  • Sundstrom, I., Bondesson, U. Hedeland, M. (2001). Identification of phase I and II metabolites of ketobemidone in patient urine using liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 763:121–131.
  • Sundstrom, I., Hedeland, M., Bondesson, U. Andren, P. E. (2002). Identification of glucuronide conjugates of ketobemidone and its phase I metabolites in human urine utilizing accurate mass and tandem time-of-flight mass spectrometry. J Mass Spectrom 37:414–420.
  • Sunwoo, Y. E., Ryu, J., Jung, H., Kang, K., Liu, K., Yoon, Y.-R.,Lee, S.,-H., Shin J. (2004). Disposition of chlorpromazine in Korean healthy subjects with CYP2D6 wild type and *10B mutation (Abstract). Clin Pharmacol Ther 73:PII–146.
  • Surapaneni, S. S., Clay, M. P., Spangle, L. A., Paschal, J. W. Lindstrom, T. D. (1997). In vitro biotransformation and identification of human cytochrome P450 isozyme-dependent metabolism of tazofelone. Drug Metab Dispos 25:1383–1388.
  • Suzuki, A., Otani, K., Mihara, K., Yasui, N., Kaneko, S., Inoue, Y. Hayashi, K. (1997). Effects of the CYP2D6 genotype on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese schizophrenic patients. Pharmacogenetics 7:415–418.
  • Suzuki, K., Yanagawa, T., Shibasaki, T., Kaniwa, N., Hasegawa, R. Tohkin, M. (2006). Effect of CYP2C9 genetic polymorphisms on the efficacy and pharmacokinetics of glimepiride in subjects with type 2 diabetes. Diabetes Res Clin Pract 72:148–154.
  • Svensson, U. S. Ashton, M. (1999). Identification of the human cytochrome P450 enzymes involved in the in vitro metabolism of artemisinin. Br J Clin Pharmacol 48:528–535.
  • Swainston Harrison, T., Perry, C. M. (2004). Aripiprazole: a review of its use in schizophrenia and schizoaffective disorder. Drugs 64:1715–1736.
  • Tacke, U., Leinonen, E., Lillsunde, P., Seppala, T., Arvela, P., Pelkonen, O. Ylitalo, P. (1992). Debrisoquine hydroxylation phenotypes of patients with high versus low to normal serum antidepressant concentrations. J Clin Psychopharmacol 12:262–267.
  • Taguchi, M., Fujiki, A., Iwamoto, J., Inoue, H., Tahara, K., Saigusa, K., Horiuchi, I., Oshima, Y. Hashimoto, Y. (2006). Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias. Biol Pharm Bull 29:517–521.
  • Taioli, E., Trachman, J., Chen, X., Toniolo, P. Garte, S. J. (1995). A CYP1A1 restriction fragment polymorphism is associated with breast cancer in African-American women. Cancer Res 55:3757–3758.
  • Takada, K., Arefayene, M., Desta, Z., Yarboro, C. H., Boumpas, D. T., Balow, J. E., Flockhart, D. A. Illei, G. G. (2004). Cytochrome P450 pharmacogenetics as a predictor of toxicity and clinical response to pulse cyclophosphamide in lupus nephritis. Arthritis Rheum 50:2202–2210.
  • Takahashi, H. Echizen, H. (2001). Pharmacogenetics of warfarin elimination and its clinical implications. Clin Pharmacokinet 40:587–603.
  • Takahashi, H., Kashima, T., Nomizo, Y., Muramoto, N., Shimizu, T., Nasu, K., Kubota, T., Kimura, S. Echizen, H. (1998). Metabolism of warfarin enantiomers in Japanese patients with heart disease having different CYP2C9 and CYP2C19 genotypes. Clin Pharmacol Ther 63:519–528.
  • Takahashi, H., Wilkinson, G. R., Padrini, R. Echizen, H. (2004). CYP2C9 and oral anticoagulation therapy with acenocoumarol and warfarin: similarities yet differences. Clin Pharmacol Ther 75:376–380.
  • Takanashi, K., Tainaka, H., Kobayashi, K., Yasumori, T., Hosakawa, M. Chiba, K. (2000). CYP2C9 Ile359 and Leu359 variants: enzyme kinetic study with seven substrates. Pharmacogenetics 10:95–104.
  • Takata, K., Saruwatari, J., Nakada, N., Nakagawa, M., Fukuda, K., Tanaka, F., Takenaka, S., Mihara, S., Marubayashi, T. Nakagawa, K. (2006). Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy. Eur J Clin Pharmacol 62:23–28.
  • Takimoto, C. H. (2007). Can tamoxifen therapy be optimized for patients with breast cancer on the basis of CYP2D6 activity assessments? Nat Clin Pract Oncol 4:152–153.
  • Tan, W., Chen, G. F., Xing, D. Y., Song, C. Y., Kadlubar, F. F. Lin, D. X. (2001). Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population. Int J Cancer 95:96–101.
  • Tanaka, F. (2007). UFT (tegafur and uracil) as postoperative adjuvant chemotherapy for solid tumors (carcinoma of the lung, stomach, colon/rectum, and breast): clinical evidence, mechanism of action, and future direction. Surg Today 37:923–943.
  • Tanaka, M., Ohkubo, T., Otani, K., Suzuki, A., Kaneko, S., Sugawara, K., Ryokawa, Y., Hakusui, H., Yamamori, S. Ishizaki, T. (1997). Metabolic disposition of pantoprazole, a proton pump inhibitor, in relation to S-mephenytoin 4’-hydroxylation phenotype and genotype. Clin Pharmacol Ther 62:619–628.
  • Tang-Liu, D. D. Riegelman, S. (1981). Metabolism of theophylline to caffeine in adults. Res Commun Chem Pathol Pharmacol 34:371–380.
  • Tang-Liu, D. D., Williams, R. L. Riegelman, S. (1982). Nonlinear theophylline elimination. Clin Pharmacol Ther 31:358–369.
  • Tang, C., Shou, M., Mei, Q., Rushmore, T. H. Rodrigues, A. D. (2000). Major role of human liver microsomal cytochrome P450 2C9 (CYP2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. J Pharmacol Exp Ther 293:453–459.
  • Tang, C., Shou, M., Rushmore, T. H., Mei, Q., Sandhu, P., Woolf, E. J., Rose, M. J., Gelmann, A., Greenberg, H. E., De Lepeleire, I., Van Hecken, A., De Schepper, P. J., Ebel, D. L., Schwartz, J. I. Rodrigues, A. D. (2001). In-vitro metabolism of celecoxib, a cyclooxygenase-2 inhibitor, by allelic variant forms of human liver microsomal cytochrome P450 2C9: correlation with CYP2C9 genotype and in-vivo pharmacokinetics. Pharmacogenetics 11:223–235.
  • Tang, W., Stearns, R. A., Wang, R. W., Chiu, S. H. Baillie, T. A. (1999). Roles of human hepatic cytochrome P450s 2C9 and 3A4 in the metabolic activation of diclofenac. Chem Res Toxicol 12:192–199.
  • Tanis, S. P., Parker, T. T., Colca, J. R., Fisher, R. M. Kletzein, R. F. (1996). Synthesis and biological activity of metabolites of the antidiabetic, antihyperglycemic agent pioglitazone. J Med Chem 39:5053–5063.
  • Tantry, U. S., Bliden, K. P. Gurbel, P. A. (2006). Prasugrel. Expert Opin Investig Drugs 15:1627–1633.
  • Tariot, P. N., Solomon, P. R., Morris, J. C., Kershaw, P., Lilienfeld, S. Ding, C. (2000). A 5-month, randomized, placebo-controlled trial of galantamine in AD. The Galantamine USA-10 Study Group. Neurology 54:2269–2276.
  • Tassaneeyakul, W., Birkett, D. J., Veronese, M. E., McManus, M. E., Tukey, R. H., Quattrochi, L. C., Gelboin, H. V. Miners, J. O. (1993). Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther 265:401–407.
  • Tassaneeyakul, W., Mohamed, Z., Birkett, D. J., McManus, M. E., Veronese, M. E., Tukey, R. H., Quattrochi, L. C., Gonzalez, F. J. Miners, J. O. (1992). Caffeine as a probe for human cytochromes P450: validation using cDNA-expression, immunoinhibition, and microsomal kinetic and inhibitor techniques. Pharmacogenetics 2:173–183.
  • Tateishi, T., Asoh, M., Yamaguchi, A., Yoda, T., Okano, Y. J., Koitabashi, Y. Kobayashi, S. (1999). Developmental changes in urinary elimination of theophylline and its metabolites in pediatric patients. Pediatr Res 45:66–70.
  • Tateishi, T., Watanabe, M., Kumai, T., Tanaka, M., Moriya, H., Yamaguchi, S., Satoh, T. Kobayashi, S. (2000). CYP3A is responsible for N-dealkylation of haloperidol and bromperidol and oxidation of their reduced forms by human liver microsomes. Life Sci 67:2913–2920.
  • Taube, J., Halsall, D. Baglin, T. (2000). Influence of cytochrome P-450 CYP2C9 polymorphisms on warfarin sensitivity and risk of over-anticoagulation in patients on long-term treatment. Blood 96:1816–1819.
  • Tay, J. K., Tan, C. H., Chong, S. A. Tan, E. C. (2007). Functional polymorphisms of the cytochrome P450 1A2 (CYP1A2) gene and prolonged QTc interval in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 31:1297–1302.
  • Tayeb, M. T., Clark, C., Sharp, L., Haites, N. E., Rooney, P. H., Murray, G. I., Payne, S. N. McLeod, H. L. (2002). CYP3A4 promoter variant is associated with prostate cancer risk in men with benign prostate hyperplasia. Oncol Rep 9:653–655.
  • Tenneze, L., Tarral, E., Ducloux, N. Funck-Brentano, C. (2002). Pharmacokinetics and electrocardiographic effects of a new controlled-release form of flecainide acetate: comparison with the standard form and influence of the CYP2D6 polymorphism. Clin Pharmacol Ther 72:112–122.
  • Terry, K. L., Titus-Ernstoff, L., Garner, E. O., Vitonis, A. F. Cramer, D. W. (2003). Interaction between CYP1A1 polymorphic variants and dietary exposures influencing ovarian cancer risk. Cancer Epidemiol Biomarkers Prev 12:187–190.
  • Thapar, M. M., Ashton, M., Lindegardh, N., Bergqvist, Y., Nivelius, S., Johansson, I. Bjorkman, A. (2002). Time-dependent pharmacokinetics and drug metabolism of atovaquone plus proguanil (Malarone) when taken as chemoprophylaxis. Eur J Clin Pharmacol 58:19–27.
  • Theken, K. N. Lee, C. R. (2007). Genetic variation in the cytochrome P450 epoxygenase pathway and cardiovascular disease risk. Pharmacogenomics 8:1369–1383.
  • Theuretzbacher, U., Ihle, F. Derendorf, H. (2006). Pharmacokinetic/pharmacodynamic profile of voriconazole. Clin Pharmacokinet 45:649–663.
  • Thjodleifsson, B. (2004). Review of rabeprazole in the treatment of gastro-oesophageal reflux disease. Expert Opin Pharmacother 5:137–149.
  • Thomsen, M. S., Chassard, D., Evene, E., Nielsen, K. K. Jorgensen, M. (2003). Pharmacokinetics of repaglinide in healthy caucasian and Japanese subjects. J Clin Pharmacol 43:23–28.
  • Timmer, C. J., Sitsen, J. M. Delbressine, L. P. (2000). Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet 38:461–474.
  • Timmermans, P. B., Wong, P. C., Chiu, A. T., Herblin, W. F., Benfield, P., Carini, D. J., Lee, R. J., Wexler, R. R., Saye, J. A. Smith, R. D. (1993). Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 45:205–251.
  • Tiseo, P. J., Perdomo, C. A. Friedhoff, L. T. (1998). Metabolism and elimination of 14C-donepezil in healthy volunteers: a single-dose study. Br J Clin Pharmacol 46(Supp l1):19–24.
  • Tjia, J. F., Colbert, J. Back, D. J. (1996). Theophylline metabolism in human liver microsomes: inhibition studies. J Pharmacol Exp Ther 276:912–917.
  • Todd, P. A. Beresford, R. (1986). Pirprofen. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy. Drugs 32:509–537.
  • Torchin, C. D., McNeilly, P. J., Kapetanovic, I. M., Strong, J. M. Kupferberg, H. J. (1996). Stereoselective metabolism of a new anticonvulsant drug candidate, losigamone, by human liver microsomes. Drug Metab Dispos 24:1002–1008.
  • Tornio, A., Niemi, M., Neuvonen, P. J. Backman, J. T. (2008). Trimethoprim and the CYP2C8*3 allele have opposite effects on the pharmacokinetics of pioglitazone. Drug Metab Dispos 36:73–80.
  • Toscano, C., Klein, K., Blievernicht, J., Schaeffeler, E., Saussele, T., Raimundo, S., Eichelbaum, M., Schwab, M. Zanger, U. M. (2006a). Impaired expression of CYP2D6 in intermediate metabolizers carrying the *41 allele caused by the intronic SNP 2988G>A: evidence for modulation of splicing events. Pharmacogenet Genomics 16:755–766.
  • Toscano, C., Raimundo, S., Klein, K., Eichelbaum, M., Schwab, M. Zanger, U. M. (2006b). A silent mutation (2939G>A, exon 6; CYP2D6*59) leading to impaired expression and function of CYP2D6. Pharmacogenet Genomics 16:767–770.
  • Totah, R. A. Rettie, A. E. (2005). Cytochrome P450 2C8: substrates, inhibitors, pharmacogenetics, and clinical relevance. Clin Pharmacol Ther 77:341–352.
  • Totah, R. A., Sheffels, P., Roberts, T., Whittington, D., Thummel, K. Kharasch, E. D. (2008). Role of CYP2B6 in stereoselective human methadone metabolism. Anesthesiology 108:363–374.
  • Townsend, K. P. Pratico, D. (2005). Novel therapeutic opportunities for Alzheimer’s disease: focus on nonsteroidal anti-inflammatory drugs. Faseb J 19:1592–1601.
  • Tracy, T. S., Hutzler, J. M., Haining, R. L., Rettie, A. E., Hummel, M. A. Dickmann, L. J. (2002). Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: effect on atypical kinetic metabolism profiles. Drug Metab Dispos 30:385–390.
  • Tran, V. T., Chang, R. S. Snyder, S. H. (1978). Histamine H1 receptors identified in mammalian brain membranes with [3H]mepyramine. Proc Natl Acad Sci U S A 75:6290–6294.
  • Transon, C., Leemann, T. Dayer, P. (1996). In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6, and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 50:209–215.
  • Transon, C., Leemann, T., Vogt, N. Dayer, P. (1995). In vivo inhibition profile of cytochrome P450TB (CYP2C9) by (+/-)-fluvastatin. Clin Pharmacol Ther 58:412–417.
  • Trivier, J. M., Libersa, C., Belloc, C. Lhermitte, M. (1993). Amiodarone N-deethylation in human liver microsomes: involvement of cytochrome P450 3A enzymes (first report). Life Sci 52:PL91–PL96.
  • Tsai, H. J., Liu, X., Mestan, K., Yu, Y., Zhang, S., Fang, Y., Pearson, C., Ortiz, K., Zuckerman, B., Bauchner, H., Cerda, S., Stubblefield, P. G., Xu, X. Wang, X. (2008). Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on GxE interactions and pathogenic pathways. Hum Genet 123:359–369.
  • Tseng, C. Y., Wang, S. L., Lai, M. D., Lai, M. L. Huang, J. D. (1996). Formation of morphine from codeine in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther 60:177–182.
  • Tserng, K. Y., King, K. C. Takieddine, F. N. (1981). Theophylline metabolism in premature infants. Clin Pharmacol Ther 29:594–600.
  • Tserng, K. Y., Takieddine, F. N. King, K. C. (1983). Developmental aspects of theophylline metabolism in premature infants. Clin Pharmacol Ther 33:522–528.
  • Tsuchiya, K., Gatanaga, H., Tachikawa, N., Teruya, K., Kikuchi, Y., Yoshino, M., Kuwahara, T., Shirasaka, T., Kimura, S. Oka, S. (2004). Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens. Biochem Biophys Res Commun 319:1322–1326.
  • Tsuzuki, D., Takemi, C., Yamamoto, S., Tamagake, K., Imaoka, S., Funae, Y., Kataoka, H., Shinoda, S. Narimatsu, S. (2001). Functional evaluation of cytochrome P450 2D6 with Gly42Arg substitution expressed in Saccharomyces cerevisiae. Pharmacogenetics 11:709–718.
  • Tucker, G. T. (1994). The interaction of proton pump inhibitors with cytochromes P450. Aliment Pharmacol Ther 8(Suppl 1):33–38.
  • Tucker, G. T., Lennard, M. S., Ellis, S. W., Woods, H. F., Cho, A. K., Lin, L. Y., Hiratsuka, A., Schmitz, D. A. Chu, T. Y. (1994). The demethylenation of methylenedioxymethamphetamine (“ecstasy”) by debrisoquine hydroxylase (CYP2D6). Biochem Pharmacol 47:1151–1156.
  • Tugnait, M., Hawes, E. M., McKay, G., Eichelbaum, M. Midha, K. K. (1999). Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine. Chem Biol Interact 118:171–189.
  • Turesky, R. J., Guengerich, F. P., Guillouzo, A. Langouet, S. (2002). Metabolism of heterocyclic aromatic amines by human hepatocytes and cytochrome P4501A2. Mutat Res 506–507:187–195.
  • Turgeon, J., Funck-Brentano, C., Gray, H. T., Pavlou, H. N., Prakash, C., Blair, I. A. Roden, D. M. (1991). Genetically determined stereoselective excretion of encainide in humans and electrophysiologic effects of its enantiomers in canine cardiac Purkinje fibers. Clin Pharmacol Ther 49:488–496.
  • Turgeon, J., Pare, J. R., Lalande, M., Grech-Belanger, O. Belanger, P. M. (1992). Isolation and structural characterization by spectroscopic methods of two glucuronide metabolites of mexiletine after N-oxidation and deamination. Drug Metab Dispos 20:762–769.
  • Turgeon, J., Pavlou, H. N., Wong, W., Funck-Brentano, C. Roden, D. M. (1990). Genetically determined steady-state interaction between encainide and quinidine in patients with arrhythmias. J Pharmacol Exp Ther 255:642–649.
  • Turgeon, J. Roden, D. M. (1989). Pharmacokinetic profile of encainide. Clin Pharmacol Ther 45:692–694.
  • Turner, M. J., 3rd, Fields, C. E. Everman, D. B. (1991). Evidence for superoxide formation during hepatic metabolism of tamoxifen. Biochem Pharmacol 41:1701–1705.
  • Turpeinen, M., Raunio, H. Pelkonen, O. (2006). The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo, and in silico. Curr Drug Metab 7:705–714.
  • Tushar, T., Vinod, T., Rajan, S., Shashindran, C. Adithan, C. (2007). Effect of honey on CYP3A4, CYP2D6, and CYP2C19 enzyme activity in healthy human volunteers. Basic Clin Pharmacol Toxicol 100:269–272.
  • Tyndale, R., Aoyama, T., Broly, F., Matsunaga, T., Inaba, T., Kalow, W., Gelboin, H. V., Meyer, U. A. Gonzalez, F. J. (1991). Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype. Pharmacogenetics 1:26–32.
  • Tyndale, R. F., Droll, K. P. Sellers, E. M. (1997). Genetically deficient CYP2D6 metabolism provides protection against oral opiate dependence. Pharmacogenetics 7:375–379.
  • Tyndale, R. F., Gonzalez, F. J., Hardwick, J. P., Kalow, W. Inaba, T. (1990). Sparteine metabolism capacity in human liver: structural variants of human P450IID6 as assessed by immunochemistry. Pharmacol Toxicol 67:14–18.
  • Ueng, Y. F., Shimada, T., Yamazaki, H. Guengerich, F. P. (1995). Oxidation of aflatoxin B1 by bacterial recombinant human cytochrome P450 enzymes. Chem Res Toxicol 8:218–225.
  • Ueno, K., Yamaguchi, R., Tanaka, K., Sakaguchi, M., Morishima, Y., Yamauchi, K. Iwai, A. (1996). Lack of a kinetic interaction between fluconazole and mexiletine. Eur J Clin Pharmacol 50:129–131.
  • Ujhelyi, M. R., O’Rangers, E. A., Fan, C., Kluger, J., Pharand, C. Chow, M. S. (1993). The pharmacokinetic and pharmacodynamic interaction between propafenone and lidocaine. Clin Pharmacol Ther 53:38–48.
  • Umemoto, A., Monden, Y., Komaki, K., Suwa, M., Kanno, Y., Suzuki, M., Lin, C. X., Ueyama, Y., Momen, M. A., Ravindernath, A. Shibutani, S. (1999). Tamoxifen-DNA adducts formed by alpha-acetoxytamoxifen N-oxide. Chem Res Toxicol 12:1083–1089.
  • Urichuk, L., Prior, T. I., Dursun, S. Baker, G. (2008). Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab 9:410–418.
  • Ursing, C., Wikner, J., Brismar, K. Rojdmark, S. (2003). Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2. J Endocrinol Invest 26:403–406.
  • Usami, O., Ashino, Y., Komaki, Y., Tomaki, M., Irokawa, T., Tamada, T., Hayashida, T., Teruya, K. Hattori, T. (2007). Efavirenz-induced neurological symptoms in rare homozygote CYP2B6 *2/*2 (C64T). Int J STD AIDS 18:575–576.
  • Uttamsingh, V., Lu, C., Miwa, G. Gan, L. S. (2005). Relative contributions of the five major human cytochromes P450, 1A2, 2C9, 2C19, 2D6, and 3A4 to the hepatic metabolism of the proteasome inhibitor bortezomib. Drug Metab Dispos 33:1723–1728.
  • Uzan, A., Gueremy, C. Le Fur, G. (1976a). [Absorption, distribution and excretion of (quinuclidinyl-3 methyl)-10-phenothiazine (LM 209), a new antihistamine]. Xenobiotica 6:633–648.
  • Uzan, A., Gueremy, C. Le Fur, G. (1976b). [Biotransformation of 10-(3-quinuclidinylmethyl)phenothiazine (LM 209), a new anti-allergy agent and the distribution and excretion of its metabolites]. Xenobiotica 6:649–665.
  • Van der Heijden, K. B., Smits, M. G., Van Someren, E. J., Ridderinkhof, K. R. Gunning, W. B. (2007). Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad Child Adolesc Psychiatry 46:233–241.
  • van der Weide, J., Steijns, L. S., van Weelden, M. J., de Haan K. (2001). The effect of genetic polymorphism of cytochrome P450 CYP2C9 on phenytoin dose requirement. Pharmacogenetics 11:287–291.
  • van der Weide, J., van Baalen-Benedek, E. H., Kootstra-Ros, J. E. (2005). Metabolic ratios of psychotropics as indication of cytochrome P450 2D6/2C19 genotype. Ther Drug Monit 27:478–483.
  • van Duursen, M. B., Sanderson, J. T. van den Berg, M. (2005). Cytochrome P450 1A1 and 1B1 in human blood lymphocytes are not suitable as biomarkers of exposure to dioxin-like compounds: polymorphisms and interindividual variation in expression and inducibility. Toxicol Sci 85:703–712.
  • van Heiningen, P. N., Hatorp, V., Kramer Nielsen, K., Hansen, K. T., van Lier, J. J., De Merbel, N. C., Oosterhuis, B. Jonkman, J. H. (1999). Absorption, metabolism, and excretion of a single oral dose of (14)C-repaglinide during repaglinide multiple dosing. Eur J Clin Pharmacol 55:521–525.
  • van Iersel, M. L., Henderson, C. J., Walters, D. G., Price, R. J., Wolf, C. R. Lake, B. G. (1994). Metabolism of [3-14C] coumarin by human liver microsomes. Xenobiotica 24:795–803.
  • van Kan, H. J., Groeneveld, G. J., Kalmijn, S., Spieksma, M., van den Berg, L. H. Guchelaar, H. J. (2005). Association between CYP1A2 activity and riluzole clearance in patients with amyotrophic lateral sclerosis. Br J Clin Pharmacol 59:310–313.
  • van Kan, H. J., van den Berg, L. H., Groeneveld, G. J., van der Straaten, R. J., van Vught, P. W., Lie, A. H. L. Guchelaar, H. J. (2008). Pharmacokinetics of riluzole: evidence for glucuronidation as a major metabolic pathway not associated with UGT1A1 genotype. Biopharm Drug Dispos 29:139–144.
  • van Schaik, R. H., de Wildt, S. N., Brosens, R., van Fessem, M., van den Anker, J. N. Lindemans, J. (2001). The CYP3A4*3 allele: is it really rare? Clin Chem 47:1104–1106.
  • Vandamme, N., Broly, F., Libersa, C., Courseau, C. Lhermitte, M. (1993). Stereoselective hydroxylation of mexiletine in human liver microsomes: implication of P450IID6—a preliminary report. J Cardiovasc Pharmacol 21:77–83.
  • Vanden Heuvel, J. P., Clark, G. C., Thompson, C. L., McCoy, Z., Miller, C. R., Lucier, G. W. Bell, D. A. (1993). CYP1A1 mRNA levels as a human exposure biomarker: use of quantitative polymerase chain reaction to measure CYP1A1 expression in human peripheral blood lymphocytes. Carcinogenesis 14:2003–2006.
  • VandenBranden, M., Ring, B. J., Binkley, S. N. Wrighton, S. A. (1996). Interaction of human liver cytochromes P450 in vitro with LY307640, a gastric proton pump inhibitor. Pharmacogenetics 6:81–91.
  • Varsaldi, F., Miglio, G., Scordo, M. G., Dahl, M. L., Villa, L. M., Biolcati, A. Lombardi, G. (2006). Impact of the CYP2D6 polymorphism on steady-state plasma concentrations and clinical outcome of donepezil in Alzheimer’s disease patients. Eur J Clin Pharmacol 62:721–726.
  • Veefkind, A. H., Haffmans, P. M. Hoencamp, E. (2000). Venlafaxine serum levels and CYP2D6 genotype. Ther Drug Monit 22:202–208.
  • Veenstra, D. L., Blough, D. K., Higashi, M. K., Farin, F. M., Srinouanprachan, S., Rieder, M. J. Rettie, A. E. (2005). CYP2C9 haplotype structure in European-American warfarin patients and association with clinical outcomes. Clin Pharmacol Ther 77:353–364.
  • Venkatakrishnan, K., Greenblatt, D. J., von Moltke, L. L., Schmider, J., Harmatz, J. S. Shader, R. I. (1998a). Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. J Clin Pharmacol 38:112–121.
  • Venkatakrishnan, K., Schmider, J., Harmatz, J. S., Ehrenberg, B. L., von Moltke, L. L., Graf, J. A., Mertzanis, P., Corbett, K. E., Rodriguez, M. C., Shader, R. I. Greenblatt, D. J. (2001). Relative contribution of CYP3A to amitriptyline clearance in humans: in vitro and in vivo studies. J Clin Pharmacol 41:1043–1054.
  • Venkatakrishnan, K., von Moltke, L. L., Duan, S. X., Fleishaker, J. C., Shader, R. I. Greenblatt, D. J. (1998b). Kinetic characterization and identification of the enzymes responsible for the hepatic biotransformation of adinazolam and N-desmethyladinazolam in man. J Pharm Pharmacol 50:265–274.
  • Venkatakrishnan, K., von Moltke, L. L. Greenblatt, D. J. (1998c). Relative quantities of catalytically active CYP 2C9 and 2C19 in human liver microsomes: application of the relative activity factor approach. J Pharm Sci 87:845–853.
  • Venkatakrishnan, K., von Moltke, L. L., Obach, R. S. Greenblatt, D. J. (2000). Microsomal binding of amitriptyline: effect on estimation of enzyme kinetic parameters in vitro. J Pharmacol Exp Ther 293:343–350.
  • Veronese, M. E., Mackenzie, P. I., Doecke, C. J., McManus, M. E., Miners, J. O. Birkett, D. J. (1991). Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9. Biochem Biophys Res Commun 175:1112–1118.
  • Vianna-Jorge, R., Perini, J. A., Rondinelli, E. Suarez-Kurtz, G. (2004). CYP2C9 genotypes and the pharmacokinetics of tenoxicam in Brazilians. Clin Pharmacol Ther 76:18–26.
  • Vickers, A. E., Sinclair, J. R., Zollinger, M., Heitz, F., Glanzel, U., Johanson, L. Fischer, V. (1999). Multiple cytochrome P-450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions. Drug Metab Dispos 27:1029–1038.
  • Vickers, S., Duncan, C. A., Vyas, K. P., Kari, P. H., Arison, B., Prakash, S. R., Ramjit, H. G., Pitzenberger, S. M., Stokker, G. Duggan, D. E. (1990). In vitro and in vivo biotransformation of simvastatin, an inhibitor of HMG CoA reductase. Drug Metab Dispos 18:476–483.
  • Vijayalakshmi, K., Vettriselvi, V., Krishnan, M., Shroff, S., Jayanth, V. R. Paul, S. F. (2005). Cytochrome p4501A1 gene variants as susceptibility marker for prostate cancer. Cancer Biomark 1:251–258.
  • Volotinen, M., Turpeinen, M., Tolonen, A., Uusitalo, J., Maenpaa, J. Pelkonen, O. (2007). Timolol metabolism in human liver microsomes is mediated principally by CYP2D6. Drug Metab Dispos 35:1135–1141.
  • Volz, M., Christ, O., Kellner, H. M., Kuch, H., Fehlhaber, H. W., Gantz, D., Hajdu, P. Cavagna, F. (1979). Kinetics and metabolism of clobazam in animals and man. Br J Clin Pharmacol 7(Suppl 1):41S–50S.
  • von Ahsen, N., Ritcher, M., Grupp, C., Ringe, B., Oellerich, M., Armstrong, V. W. (2001). No influence of MDR-1 C3435T polymorphism or a CYP3A4 promoter polymorphism(CYP3A4-V allele) on dose-adjusted cyclosporine A trough concentrations or rejection incidence in stable renal transplant recipients. Clin Chem 47:1048–1052.
  • von Bahr, C., Movin, G., Nordin, C., Liden, A., Hammarlund-Udenaes, M., Hedberg, A., Ring, H., Sjoqvist, F. (1991). Plasma levels of thioridazine and metabolites are influenced by the debrisoquin hydroxylation phenotype. Clin Pharmacol Ther 49:234–240.
  • von Bahr, C., Ursing, C., Yasui, N., Tybring, G., Bertilsson, L., Rojdmark, S. (2000). Fluvoxamine, but not citalopram, increases serum melatonin in healthy subjects—an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 56:123–127.
  • von Moltke, L. L., Greenblatt, D. J., Duan, S. X., Schmider, J., Wright, C. E., Harmatz, J. S. Shader, R. I. (1997). Human cytochromes mediating N-demethylation of fluoxetine in vitro. Psychopharmacology (Berl) 132:402–407.
  • von Moltke, L. L., Greenblatt, D. J., Giancarlo, G. M., Granda, B. W., Harmatz, J. S. Shader, R. I. (2001a). Escitalopram (S-citalopram) and its metabolites in vitro: cytochromes mediating biotransformation, inhibitory effects, and comparison to R-citalopram. Drug Metab Dispos 29:1102–1109.
  • von Moltke, L. L., Greenblatt, D. J., Granda, B. W., Giancarlo, G. M., Duan, S. X., Daily, J. P., Harmatz, J. S. Shader, R. I. (2001b). Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse-transcriptase inhibitors. J Clin Pharmacol 41:85–91.
  • von Philipsborn, G., Gries, J., Hofmann, H. P., Kreiskott, H., Kretzschmar, R., Muller, C. D., Raschack, M. Teschendorf, H. J. (1984). Pharmacological studies on propafenone and its main metabolite 5-hydroxypropafenone. Arzneimittelforschung 34:1489–1497.
  • von Richter, O., Burk, O., Fromm, M. F., Thon, K. P., Eichelbaum, M. Kivisto, K. T. (2004a). Cytochrome P450 3A4 and P-glycoprotein expression in human small intestinal enterocytes and hepatocytes: a comparative analysis in paired tissue specimens. Clin Pharmacol Ther 75:172–183.
  • von Richter, O., Greiner, B., Fromm, M. F., Fraser, R., Omari, T., Barclay, M. L., Dent, J., Somogyi, A. A. Eichelbaum, M. (2001). Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique. Clin Pharmacol Ther 70:217–227.
  • von Richter O., Pitarque, M., Rodriguez-Antona, C., Testa, A., Mantovani, R., Oscarson, M., Ingelman-Sundberg, M. (2004b). Polymorphic NF-Y dependent regulation of human nicotine C-oxidase (CYP2A6). Pharmacogenetics 14:369–379.
  • von Weymarn, L. B. Murphy, S. E. (2003). CYP2A13-catalysed coumarin metabolism: comparison with CYP2A5 and CYP2A6. Xenobiotica 33:73–81.
  • Vormfelde, S. V., Engelhardt, S., Zirk, A., Meineke, I., Tuchen, F., Kirchheiner, J. Brockmoller, J. (2004). CYP2C9 polymorphisms and the interindividual variability in pharmacokinetics and pharmacodynamics of the loop diuretic drug torsemide. Clin Pharmacol Ther 76:557–566.
  • Vree, T. B., Lagerwerf, A. J., Bleeker, C. P. de Grood, P. M. (1999). Direct high-performance liquid chromatography determination of propofol and its metabolite quinol with their glucuronide conjugates and preliminary pharmacokinetics in plasma and urine of man. J Chromatogr B Biomed Sci Appl 721:217–228.
  • Waade, R. B., Christensen, H., Rudberg, I., Refsum, H. Hermann, M. (2009). Influence of comedication on serum concentrations of aripiprazole and dehydroaripiprazole. Ther Drug Monit 31:231–238.
  • Wagner, F., Kalusche, D., Trenk, D., Jahnchen, E. Roskamm, H. (1987). Drug interaction between propafenone and metoprolol. Br J Clin Pharmacol 24:213–220.
  • Wagner, M. L. Landis, B. E. (1997). Riluzole: a new agent for amyotrophic lateral sclerosis. Ann Pharmacother 31:738–744.
  • Wagstaff, A. J. Goa, K. L. (2002). Rosiglitazone: a review of its use in the management of type 2 diabetes mellitus. Drugs 62:1805–1837.
  • Walsh, T. J., Karlsson, M. O., Driscoll, T., Arguedas, A. G., Adamson, P., Saez-Llorens, X., Vora, A. J., Arrieta, A. C., Blumer, J., Lutsar, I., Milligan, P. Wood, N. (2004). Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration. Antimicrob Agents Chemother 48:2166–2172.
  • Walter, H. Lubben, G. (2005). Potential role of oral thiazolidinedione therapy in preserving beta-cell function in type 2 diabetes mellitus. Drugs 65:1–13.
  • Wan, J., Imaoka, S., Chow, T., Hiroi, T., Yabusaki, Y. Funae, Y. (1997). Expression of four rat CYP2D isoforms in Saccharomyces cerevisiae and their catalytic specificity. Arch Biochem Biophys 348:383–390.
  • Wandel, C., Witte, J. S., Hall, J. M., Stein, C. M., Wood, A. J. Wilkinson, G. R. (2000). CYP3A activity in African-American and European-American men: population differences and functional effect of the CYP3A4*1B 5’-promoter region polymorphism. Clin Pharmacol Ther 68:82–91.
  • Wang, B., Sanchez, R. I., Franklin, R. B., Evans, D. C. Huskey, S. E. (2004). The involvement of CYP3A4 and CYP2C9 in the metabolism of 17 alpha-ethinylestradiol. Drug Metab Dispos 32:1209–1212.
  • Wang, G., Zhang, H., He, F. Fang, X. (2006a). Effect of the CYP2D6*10 C188T polymorphism on postoperative tramadol analgesia in a Chinese population. Eur J Clin Pharmacol 62:927–931.
  • Wang, H., Tan, W., Hao, B., Miao, X., Zhou, G., He, F. Lin, D. (2003). Substantial reduction in risk of lung adenocarcinoma associated with genetic polymorphism in CYP2A13, the most active cytochrome P450 for the metabolic activation of tobacco-specific carcinogen NNK. Cancer Res 63:8057–8061.
  • Wang, J., Sonnerborg, A., Rane, A., Josephson, F., Lundgren, S., Stahle, L. Ingelman-Sundberg, M. (2006b). Identification of a novel specific CYP2B6 allele in Africans causing impaired metabolism of the HIV drug efavirenz. Pharmacogenet Genomics 16:191–198.
  • Wang, J. H., Liu, Z. Q., Wang, W., Chen, X. P., Shu, Y., He, N. Zhou, H. H. (2001). Pharmacokinetics of sertraline in relation to genetic polymorphism of CYP2C19. Clin Pharmacol Ther 70:42–47.
  • Wang, J. S., Backman, J. T., Taavitsainen, P., Neuvonen, P. J. Kivisto, K. T. (2000). Involvement of CYP1A2 and CYP3A4 in lidocaine N-deethylation and 3-hydroxylation in humans. Drug Metab Dispos 28:959–965.
  • Wang, J. S. DeVane, C. L. (2003). Involvement of CYP3A4, CYP2C8, and CYP2D6 in the metabolism of (R)- and (S)-methadone in vitro. Drug Metab Dispos 31:742–747.
  • Wang, J. S., Neuvonen, M., Wen, X., Backman, J. T. Neuvonen, P. J. (2002a). Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Drug Metab Dispos 30:1352–1356.
  • Wang, L. L., Li, Y. Zhou, S. F. (2009). A bioinformatics approach for the phenotype prediction of nonsynonymous single-nucleotide polymorphisms in human cytochrome P450s. Drug Metab Dispos doi: 10.1124/dmd.108.026047.
  • Wang, R., Chen, K., Wen, S. Y., Li, J. Wang, S. Q. (2005). Pharmacokinetics of glimepiride and cytochrome P450 2C9 genetic polymorphisms. Clin Pharmacol Ther 78:90–92.
  • Wang, R. W., Kari, P. H., Lu, A. Y., Thomas, P. E., Guengerich, F. P. Vyas, K. P. (1991). Biotransformation of lovastatin. IV. Identification of cytochrome P450 3A proteins as the major enzymes responsible for the oxidative metabolism of lovastatin in rat and human liver microsomes. Arch Biochem Biophys 290:355–361.
  • Wang, R. W., Liu, L. Cheng, H. (1996). Identification of human liver cytochrome P450 isoforms involved in the in vitro metabolism of cyclobenzaprine. Drug Metab Dispos 24:786–791.
  • Wang, S. L., He, X. Y., Shen, J., Wang, J. S. Hong, J. Y. (2006c). The missense genetic polymorphisms of human CYP2A13: functional significance in carcinogen activation and identification of a null allelic variant. Toxicol Sci 94:38–45.
  • Wang, S. L., Huang, J., Lai, M. D. Tsai, J. J. (1995). Detection of CYP2C9 polymorphism based on the polymerase chain reaction in Chinese. Pharmacogenetics 5:37–42.
  • Wang, S. L., Huang, J. D., Lai, M. D., Liu, B. H. Lai, M. L. (1993). Molecular basis of genetic variation in debrisoquin hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6. Clin Pharmacol Ther 53:410–418.
  • Wang, S. L., Lai, M. D. Huang, J. D. (1999). G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese. Drug Metab Dispos 27:385–388.
  • Wang, T., Roden, D. M., Wolfenden, H. T., Woosley, R. L., Wood, A. J. Wilkinson, G. R. (1984). Influence of genetic polymorphism on the metabolism and disposition of encainide in man. J Pharmacol Exp Ther 228:605–611.
  • Wang, X., Zuckerman, B., Pearson, C., Kaufman, G., Chen, C., Wang, G., Niu, T., Wise, P. H., Bauchner, H. Xu, X. (2002b). Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight. JAMA 287:195–202.
  • Wang, X. D., Li, J. L., Su, Q. B., Deng, X. Y., Lu, Y., Chen, J., Zhang, J. X., Zhao, L. Z., Zuo, Z., Chan, E., Chen, X., Chowbay, B., Xue, C. C., Huang, M. Zhou, S. F. (2007). A pharmacogenetic study of pregnane X receptor (NR1I2) in Han Chinese. Curr Drug Metab 8:778–786.
  • Wanwimolruk, S., Bhawan, S., Coville, P. F. Chalcroft, S. C. (1998). Genetic polymorphism of debrisoquine (CYP2D6) and proguanil (CYP2C19) in South Pacific Polynesian populations. Eur J Clin Pharmacol 54:431–435.
  • Ward, B. A., Gorski, J. C., Jones, D. R., Hall, S. D., Flockhart, D. A. Desta, Z. (2003). The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther 306:287–300.
  • Ward, S. A., Helsby, N. A., Skjelbo, E., Brosen, K., Gram, L. F. Breckenridge, A. M. (1991). The activation of the biguanide antimalarial proguanil co-segregates with the mephenytoin oxidation polymorphism—a panel study. Br J Clin Pharmacol 31:689–692.
  • Watanabe, Y., Nakajima, M. Yokoi, T. (2002). Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos 30:1462–1469.
  • Watkins, P. B. Whitcomb, R. W. (1998). Hepatic dysfunction associated with troglitazone. N Engl J Med 338:916–917.
  • Waxman, D. J., Attisano, C., Guengerich, F. P. Lapenson, D. P. (1988). Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6 beta-hydroxylase cytochrome P-450 enzyme. Arch Biochem Biophys 263:424–436.
  • Wei, L., Locuson, C. W. Tracy, T. S. (2007). Polymorphic variants of CYP2C9: mechanisms involved in reduced catalytic activity. Mol Pharmacol 72:1280–1288.
  • Weinshilboum, R. (2003). Inheritance and drug response. N Engl J Med 348:529–537.
  • Welfare, M. R., Aitkin, M., Bassendine, M. F. Daly, A. K. (1999). Detailed modelling of caffeine metabolism and examination of the CYP1A2 gene: lack of a polymorphism in CYP1A2 in Caucasians. Pharmacogenetics 9:367–375.
  • Wen, S. Y., Wang, H., Sun, O. J. Wang, S. Q. (2003). Rapid detection of the known SNPs of CYP2C9 using oligonucleotide microarray. World J Gastroenterol 9:1342–1346.
  • Wennerholm, A., Dandara, C., Sayi, J., Svensson, J. O., Abdi, Y. A., Ingelman-Sundberg, M., Bertilsson, L., Hasler, J. Gustafsson, L. L. (2002). The African-specific CYP2D617 allele encodes an enzyme with changed substrate specificity. Clin Pharmacol Ther 71:77–88.
  • Wennerholm, A., Johansson, I., Hidestrand, M., Bertilsson, L., Gustafsson, L. L. Ingelman-Sundberg, M. (2001). Characterization of the CYP2D6*29 allele commonly present in a black Tanzanian population causing reduced catalytic activity. Pharmacogenetics 11:417–427.
  • Wennerholm, A., Johansson, I., Massele, A. Y., Lande, M., Alm, C., Aden-Abdi, Y., Dahl, M. L., Ingelman-Sundberg, M., Bertilsson, L. Gustafsson, L. L. (1999). Decreased capacity for debrisoquine metabolism among black Tanzanians: analyses of the CYP2D6 genotype and phenotype. Pharmacogenetics 9:707–714.
  • Werner, U., Werner, D., Pahl, A., Mundkowski, R., Gillich, M. Brune, K. (2002). Investigation of the pharmacokinetics of celecoxib by liquid chromatography-mass spectrometry. Biomed Chromatogr 16:56–60.
  • Wester, M. R., Lasker, J. M., Johnson, E. F. Raucy, J. L. (2000). CYP2C19 participates in tolbutamide hydroxylation by human liver microsomes. Drug Metab Dispos 28:354–359.
  • Westlind-Johnsson, A., Hermann, R., Huennemeyer, A., Hauns, B., Lahu, G., Nassr, N., Zech, K., Ingelman-Sundberg, M. von Richter O. (2006). Identification and characterization of CYP3A4*20, a novel rare CYP3A4 allele without functional activity. Clin Pharmacol Ther 79:339–349.
  • Westlind, A., Lofberg, L., Tindberg, N., Andersson, T. B. Ingelman-Sundberg, M. (1999). Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5’-upstream regulatory region. Biochem Biophys Res Commun 259:201–205.
  • Westra, P., van Thiel, M. J., Vermeer, G. A., Soeterbroek, A. M., Scaf, A. H. Claessens, H. A. (1986). Pharmacokinetics of galanthamine (a long-acting anticholinesterase drug) in anaesthetized patients. Br J Anaesth 58:1303–1307.
  • White, I. N. (2003). Tamoxifen: is it safe? Comparison of activation and detoxication mechanisms in rodents and in humans. Curr Drug Metab 4:223–239.
  • White, J. A., Beckett-Jones, B., Guo, Y. D., Dilworth, F. J., Bonasoro, J., Jones, G. Petkovich, M. (1997). cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450. J Biol Chem 272:18538–18541.
  • Whyte, E. M., Romkes, M., Mulsant, B. H., Kirshne, M. A., Begley, A. E., Reynolds, C. F.3rd, Pollock, B. G. (2006). CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly. Int J Geriatr Psychiatry 21:542–549.
  • Wickremsinhe, E. R., Tian, Y., Ruterbories, K. J., Verburg, E. M., Weerakkody, G. J., Kurihara, A. Farid, N. A. (2007). Stereoselective metabolism of prasugrel in humans using a novel chiral liquid chromatography-tandem mass spectrometry method. Drug Metab Dispos 35:917–921.
  • Wiebe, V. J., Osborne, C. K., McGuire, W. L. DeGregorio, M. W. (1992). Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. J Clin Oncol 10:990–994.
  • Wilcock, G. K., Lilienfeld, S. Gaens, E. (2000). Efficacy and safety of galantamine in patients with mild to moderate Alzheimer’s disease: multicentre, randomised, controlled trial. Galantamine International-1 Study Group. BMJ 321:1445–1449.
  • Wild, M. J., McKillop, D. Butters, C. J. (1999). Determination of the human cytochrome P450 isoforms involved in the metabolism of zolmitriptan. Xenobiotica 29:847–857.
  • Wilder-Smith, C. H., Hufschmid, E. Thormann, W. (1998). The visceral and somatic antinociceptive effects of dihydrocodeine and its metabolite, dihydromorphine. A cross-over study with extensive and quinidine-induced poor metabolizers. Br J Clin Pharmacol 45:575–581.
  • Wilkinson, G. R. (2005). Drug metabolism and variability among patients in drug response. N Engl J Med 352:2211–2221.
  • Willey, J. C., Coy, E. L., Frampton, M. W., Torres, A., Apostolakos, M. J., Hoehn, G., Schuermann, W. H., Thilly, W. G., Olson, D. E., Hammersley, J. R., Crespi, C. L. Utell, M. J. (1997). Quantitative RT-PCR measurement of cytochromes p450 1A1, 1B1, and 2B7, microsomal epoxide hydrolase, and NADPH oxidoreductase expression in lung cells of smokers and nonsmokers. Am J Respir Cell Mol Biol 17:114–124.
  • Williams, E. T., Jones, K. O., Ponsler, G. D., Lowery, S. M., Perkins, E. J., Wrighton, S. A., Ruterbories, K. J., Kazui, M. Farid, N. A. (2008). The biotransformation of prasugrel, a new thienopyridine prodrug, by the human carboxylesterases 1 and 2. Drug Metab Dispos 36:1227–1232.
  • Williams, M. L., Lennard, M. S., Martin, I. J. Tucker, G. T. (1994). Interindividual variation in the isomerization of 4-hydroxytamoxifen by human liver microsomes: involvement of cytochromes P450. Carcinogenesis 15:2733–2738.
  • Williams, P. A., Cosme, J., Sridhar, V., Johnson, E. F. McRee, D. E. (2000). Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity. Mol Cell 5:121–131.
  • Wirth, K. E., Breithardt, G. Michaelis, L. (1983). [Detection of aprindine and its metabolites in plasma and urine]. Herz 8:302–308.
  • Wiseman, L. R. Faulds, D. (1995). Oral pilocarpine: a review of its pharmacological properties and clinical potential in xerostomia. Drugs 49:143–155.
  • Wojcikowski, J., Maurel, P. Daniel, W. A. (2006). Characterization of human cytochrome p450 enzymes involved in the metabolism of the piperidine-type phenothiazine neuroleptic thioridazine. Drug Metab Dispos 34:471–476.
  • Wojcikowski, J., Pichard-Garcia, L., Maurel, P. Daniel, W. A. (2003). Contribution of human cytochrome p-450 isoforms to the metabolism of the simplest phenothiazine neuroleptic promazine. Br J Pharmacol 138:1465–1474.
  • Wokke, J. (1996). Riluzole. Lancet 348:795–799.
  • Wong, H. L., Murphy, S. E. Hecht, S. S. (2005). Cytochrome P450 2A- catalyzed metabolic activation of structurally similar carcinogenic nitrosamines: N’-nitrosonornicotine enantiomers, N-nitrosopiperidine, and N-nitrosopyrrolidine. Chem Res Toxicol 18:61–69.
  • Wong, M., Balleine, R. L., Collins, M., Liddle, C., Clarke, C. L. Gurney, H. (2004). CYP3A5 genotype and midazolam clearance in Australian patients receiving chemotherapy. Clin Pharmacol Ther 75:529–538.
  • Woo, S. I., Kim, J. W., Seo, H. G., Park, C. H., Han, S. H., Kim, S. H., Kim, K. W., Jhoo, J. H. Woo, J. I. (2001). CYP2D6*4 polymorphism is not associated with Parkinson’’s disease and has no protective role against Alzheimer’s disease in the Korean population. Psychiatry Clin Neurosci 55:373–377.
  • Woolhouse, N. M., Andoh, B., Mahgoub, A., Sloan, T. P., Idle, J. R. Smith, R. L. (1979). Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. Clin Pharmacol Ther 26:584–591.
  • Woosley, R. L., Roden, D. M., Dai, G. H., Wang, T., Altenbern, D., Oates, J. Wilkinson, G. R. (1986). Coinheritance of the polymorphic metabolism of encainide and debrisoquin. Clin Pharmacol Ther 39:282–287.
  • Wu, D., Otton, S. V., Inaba, T., Kalow, W. Sellers, E. M. (1997). Interactions of amphetamine analogs with human liver CYP2D6. Biochem Pharmacol 53:1605–1612.
  • Wu, Z. L., Huang, S. L., Ou-Yang, D. S., Xu, Z. H., Xie, H. G. Zhou, H. H. (1998). Clomipramine N-demethylation metabolism in human liver microsomes. Zhongguo Yao Li Xue Bao 19:433–436.
  • Wuttke, H., Rau, T., Heide, R., Bergmann, K., Bohm, M., Weil, J., Werner, D. Eschenhagen, T. (2002). Increased frequency of cytochrome P450 2D6 poor metabolizers among patients with metoprolol-associated adverse effects. Clin Pharmacol Ther 72:429–437.
  • Wyen, C., Hendra, H., Vogel, M., Hoffmann, C., Knechten, H., Brockmeyer, N. H., Bogner, J. R., Rockstroh, J., Esser, S., Jaeger, H., Harrer, T., Mauss, S., van Lunzen, J., Skoetz, N., Jetter, A., Groneuer, C., Fatkenheuer, G., Khoo, S. H., Egan, D., Back, D. J. Owen, A. (2008). Impact of CYP2B6 983T>C polymorphism on non-nucleoside reverse transcriptase inhibitor plasma concentrations in HIV-infected patients. J Antimicrob Chemother 61:914–918.
  • Wynne, H. A., Long, A., Nicholson, E., Ward, A. Keir, D. (1998). Are altered pharmacokinetics of nonsteroidal anti-inflammatory drugs (NSAIDs) a risk factor for gastrointestinal bleeding? Br J Clin Pharmacol 45:405–408.
  • Xiao, Z. S., Goldstein, J. A., Xie, H. G., Blaisdell, J., Wang, W., Jiang, C. H., Yan, F. X., He, N., Huang, S. L., Xu, Z. H. Zhou, H. H. (1997). Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele. J Pharmacol Exp Ther 281:604–609.
  • Xie, H. G., Kim, R. B., Stein, C. M., Wilkinson, G. R. Wood, A. J. (1999a). Genetic polymorphism of (S)-mephenytoin 4’’-hydroxylation in populations of African descent. Br J Clin Pharmacol 48:402–408.
  • Xie, H. G., Stein, C. M., Kim, R. B., Wilkinson, G. R., Flockhart, D. A. Wood, A. J. (1999b). Allelic, genotypic, and phenotypic distributions of S-mephenytoin 4’-hydroxylase (CYP2C19) in healthy Caucasian populations of European descent throughout the world. Pharmacogenetics 9:539–549.
  • Xie, H. G., Xu, Z. H., Luo, X., Huang, S. L., Zeng, F. D. Zhou, H. H. (1996). Genetic polymorphisms of debrisoquine and S-mephenytoin oxidation metabolism in Chinese populations: a meta-analysis. Pharmacogenetics 6:235–238.
  • Xie, H. J., Yasar, U., Lundgren, S., Griskevicius, L., Terelius, Y., Hassan, M. Rane, A. (2003). Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation. Pharmacogenomics J 3:53–61.
  • Xu, B. Y., Guo, L. P., Lee, S. S., Dong, Q. M., Tan, Y., Yao, H., Li, L. H., Lin, C. K., Kung, H. F. He, M. L. (2007). Genetic variability of CYP2B6 polymorphisms in four southern Chinese populations. World J Gastroenterol 13:2100–2103.
  • Xu, C., Rao, Y. S., Xu, B., Hoffmann, E., Jones, J., Sellers, E. M. Tyndale, R. F. (2002). An in vivo pilot study characterizing the new CYP2A6*7, *8, and *10 alleles. Biochem Biophys Res Commun 290:318–324.
  • Xu, X., Kelsey, K. T., Wiencke, J. K., Wain, J. C. Christiani, D. C. (1996). Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility. Cancer Epidemiol Biomarkers Prev 5:687–692.
  • Xu, Y., Sun, Y., Yao, L., Shi, L., Wu, Y., Ouyang, T., Li, J., Wang, T., Fan, Z., Fan, T., Lin, B., He, L., Li, P. Xie, Y. (2008). Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment. Ann Oncol 19:1423–1429.
  • Xu, Z. H., Wang, W., Zhao, X. J., Huang, S. L., Zhu, B., He, N., Shu, Y., Liu, Z. Q. Zhou, H. H. (1999). Evidence for involvement of polymorphic CYP2C19 and 2C9 in the N-demethylation of sertraline in human liver microsomes. Br J Clin Pharmacol 48:416–423.
  • Yager, J. D. Liehr, J. G. (1996). Molecular mechanisms of estrogen carcinogenesis. Annu Rev Pharmacol Toxicol 36:203–232.
  • Yamamoto, Y., Tasaki, T., Nakamura, A., Iwata, H., Kazusaka, A., Gonzalez, F. J. Fujita, S. (1998). Molecular basis of the Dark Agouti rat drug oxidation polymorphism: importance of CYP2D1 and CYP2D2. Pharmacogenetics 8:73–82.
  • Yamanaka, H., Nakajima, M., Fukami, T., Sakai, H., Nakamura, A., Katoh, M., Takamiya, M., Aoki, Y. Yokoi, T. (2005a). CYP2A6 and CYP2B6 are involved in nornicotine formation from nicotine in humans: interindividual differences in these contributions. Drug Metab Dispos 33:1811–1818.
  • Yamanaka, H., Nakajima, M., Katoh, M., Kanoh, A., Tamura, O., Ishibashi, H. Yokoi, T. (2005b). trans-3’-hydroxycotinine O- and N-glucuronidations in human liver microsomes. Drug Metab Dispos 33:23–30.
  • Yamano, H. O., Matsushita, H. O. Yanagiwara, S. (2008). Plasma concentration of rabeprazole after 8-week administration in gastroesophageal reflux disease patients and intragastric pH elevation. J Gastroenterol Hepatol 23:534–540.
  • Yamano, S., Nhamburo, P. T., Aoyama, T., Meyer, U. A., Inaba, T., Kalow, W., Gelboin, H. V., McBride, O. W. Gonzalez, F. J. (1989). cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver. Biochemistry 28:7340–7348.
  • Yamano, S., Tatsuno, J. Gonzalez, F. J. (1990). The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. Biochemistry 29:1322–1329.
  • Yamato, C., Takahashi, T. Fujita, T. (1974). Studies on metabolism of trazodone. I. Metabolic fate of (14C)trazodone hydrochloride in rats. Xenobiotica 4:313–326.
  • Yamato, C., Takahashi, T. Fujita, T. (1976). Studies on metabolism of trazodone. III Species differences. Xenobiotica 6:295–306.
  • Yamazaki, H., Guo, Z., Persmark, M., Mimura, M., Inoue, K., Guengerich, F. P. Shimada, T. (1994a). Bufuralol hydroxylation by cytochrome P450 2D6 and 1A2 enzymes in human liver microsomes. Mol Pharmacol 46:568–577.
  • Yamazaki, H., Inoue, K., Chiba, K., Ozawa, N., Kawai, T., Suzuki, Y., Goldstein, J. A., Guengerich, F. P. Shimada, T. (1998a). Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochem Pharmacol 56:243–251.
  • Yamazaki, H., Inoue, K., Hashimoto, M. Shimada, T. (1999a). Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol 73:65–70.
  • Yamazaki, H., Inoue, K., Mimura, M., Oda, Y., Guengerich, F. P. Shimada, T. (1996). 7-ethoxycoumarin O-deethylation catalyzed by cytochromes P450 1A2 and 2E1 in human liver microsomes. Biochem Pharmacol 51:313–319.
  • Yamazaki, H., Inui, Y., Yun, C. H., Guengerich, F. P. Shimada, T. (1992). Cytochrome P450 2E1 and 2A6 enzymes as major catalysts for metabolic activation of N-nitrosodialkylamines and tobacco-related nitrosamines in human liver microsomes. Carcinogenesis 13:1789–1794.
  • Yamazaki, H., Kiyotani, K., Tsubuko, S., Matsunaga, M., Fujieda, M., Saito, T., Miura, J., Kobayashi, S. Kamataki, T. (2003). Two novel haplotypes of CYP2D6 gene in a Japanese population. Drug Metab Pharmacokinet 18:269–271.
  • Yamazaki, H., Mimura, M., Sugahara, C. Shimada, T. (1994b). Catalytic roles of rat and human cytochrome P450 2A enzymes in testosterone 7 alpha- and coumarin 7-hydroxylations. Biochem Pharmacol 48:1524–1527.
  • Yamazaki, H., Shaw, P. M., Guengerich, F. P. Shimada, T. (1998b). Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes. Chem Res Toxicol 11:659–665.
  • Yamazaki, H., Shibata, A., Suzuki, M., Nakajima, M., Shimada, N., Guengerich, F. P. Yokoi, T. (1999b). Oxidation of troglitazone to a quinone-type metabolite catalyzed by cytochrome P-450 2C8 and P-450 3A4 in human liver microsomes. Drug Metab Dispos 27:1260–1266.
  • Yamazaki, H. Shimada, T. (1997). Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys 346:161–169.
  • Yamazaki, H., Suzuki, M., Tane, K., Shimada, N., Nakajima, M. Yokoi, T. (2000). In vitro inhibitory effects of troglitazone and its metabolites on drug oxidation activities of human cytochrome P450 enzymes: comparison with pioglitazone and rosiglitazone. Xenobiotica 30:61–70.
  • Yamazaki, S., Sato, K., Suhara, K., Sakaguchi, M., Mihara, K. Omura, T. (1993). Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. J Biochem 114:652–657.
  • Yanagihara, Y., Kariya, S., Ohtani, M., Uchino, K., Aoyama, T., Yamamura, Y. Iga, T. (2001). Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. Drug Metab Dispos 29:887–890.
  • Yang, T. J., Shou, M., Korzekwa, K. R., Gonzalez, F. J., Gelboin, H. V. Yang, S. K. (1998). Role of cDNA-expressed human cytochromes P450 in the metabolism of diazepam. Biochem Pharmacol 55:889–896.
  • Yanni, S. B., Annaert, P. P., Augustijns, P., Bridges, A., Gao, Y., Benjamin, D. K., Jr, Thakker, D. R. (2008). Role of flavin-containing monooxygenase in oxidative metabolism of voriconazole by human liver microsomes. Drug Metab Dispos 36:1119–1125.
  • Yano, J. K., Hsu, M. H., Griffin, K. J., Stout, C. D. Johnson, E. F. (2005). Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat Struct Mol Biol 12:822–823.
  • Yasar, U., Annas, A., Svensson, J. O., Lazorova, L., Artursson, P. Al-Shurbaji, A. (2005). Ketobemidone is a substrate for cytochrome P4502C9 and 3A4, but not for P-glycoprotein. Xenobiotica 35:785–796.
  • Yasar, U., Bennet, A. M., Eliasson, E., Lundgren, S., Wiman, B., De Faire, U., Rane, A. (2003). Allelic variants of cytochromes P450 2C modify the risk for acute myocardial infarction. Pharmacogenetics 13:715–720.
  • Yasar, U., Eliasson, E., Dahl, M. L., Johansson, I., Ingelman-Sundberg, M. Sjoqvist, F. (1999). Validation of methods for CYP2C9 genotyping: frequencies of mutant alleles in a Swedish population. Biochem Biophys Res Commun 254:628–631.
  • Yasar, U., Eliasson, E., Forslund-Bergengren, C., Tybring, G., Gadd, M., Sjoqvist, F. Dahl, M. L. (2001a). The role of CYP2C9 genotype in the metabolism of diclofenac in vivo and in vitro. Eur J Clin Pharmacol 57:729–735.
  • Yasar, U., Forslund-Bergengren, C., Tybring, G., Dorado, P., Llerena, A., Sjoqvist, F., Eliasson, E. Dahl, M. L. (2002a). Pharmacokinetics of losartan and its metabolite E-3174 in relation to the CYP2C9 genotype. Clin Pharmacol Ther 71:89–98.
  • Yasar, U., Lundgren, S., Eliasson, E., Bennet, A., Wiman, B., de Faire, U., Rane, A. (2002b). Linkage between the CYP2C8 and CYP2C9 genetic polymorphisms. Biochem Biophys Res Commun 299:25–28.
  • Yasar, U., Tybring, G., Hidestrand, M., Oscarson, M., Ingelman-Sundberg, M., Dahl, M. L. Eliasson, E. (2001b). Role of CYP2C9 polymorphism in losartan oxidation. Drug Metab Dispos 29:1051–1056.
  • Yasuda, S. U., Wellstein, A., Likhari, P., Barbey, J. T. Woosley, R. L. (1995). Chlorpheniramine plasma concentration and histamine H1-receptor occupancy. Clin Pharmacol Ther 58:210–220.
  • Yasuda, S. U., Zannikos, P., Young, A. E., Fried, K. M., Wainer, I. W. Woosley, R. L. (2002). The roles of CYP2D6 and stereoselectivity in the clinical pharmacokinetics of chlorpheniramine. Br J Clin Pharmacol 53:519–525.
  • Yasui-Furukori, N., Hidestrand, M., Spina, E., Facciola, G., Scordo, M. G. Tybring, G. (2001). Different enantioselective 9-hydroxylation of risperidone by the two human CYP2D6 and CYP3A4 enzymes. Drug Metab Dispos 29:1263–1268.
  • Yasui, N., Tybring, G., Otani, K., Mihara, K., Suzuki, A., Svensson, J. O. Kaneko, S. (1997). Effects of thioridazine, an inhibitor of CYP2D6, on the steady-state plasma concentrations of the enantiomers of mianserin and its active metabolite, desmethylmianserin, in depressed Japanese patients. Pharmacogenetics 7:369–374.
  • Yasumori, T., Li, Q. H., Yamazoe, Y., Ueda, M., Tsuzuki, T. Kato, R. (1994). Lack of low Km diazepam N-demethylase in livers of poor metabolizers for S-mephenytoin 4’-hydroxylation. Pharmacogenetics 4:323–331.
  • Yasumori, T., Murayama, N., Yamazoe, Y. Kato, R. (1990). Polymorphism in hydroxylation of mephenytoin and hexobarbital stereoisomers in relation to hepatic P-450 human-2. Clin Pharmacol Ther 47:313–322.
  • Yasumori, T., Nagata, K., Yang, S. K., Chen, L. S., Murayama, N., Yamazoe, Y. Kato, R. (1993). Cytochrome P450– mediated metabolism of diazepam in human and rat: involvement of human CYP2C in N-demethylation in the substrate concentration-dependent manner. Pharmacogenetics 3:291–301.
  • Yatham, L. N. (2002). The role of novel antipsychotics in bipolar disorders. J Clin Psychiatry 63:10–14.
  • Yeh, S. Y., Gorodetzky, C. W. Krebs, H. A. (1977). Isolation and identification of morphine 3- and 6-glucuronides, morphine 3,6-diglucuronide, morphine 3-ethereal sulfate, normorphine, and normorphine 6-glucuronide as morphine metabolites in humans. J Pharm Sci 66:1288–1293.
  • Yeleswaram, K., Vachharajani, N. Santone, K. (1999). Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 26:190–191.
  • Yin, O. Q., Shi, X. J., Tomlinson, B. Chow, M. S. (2005a). Effect of CYP2D6*10 allele on the pharmacokinetics of loratadine in chinese subjects. Drug Metab Dispos 33:1283–1287.
  • Yin, O. Q., Tomlinson, B. Chow, M. S. (2005b). CYP2C9, but not CYP2C19, polymorphisms affect the pharmacokinetics and pharmacodynamics of glyburide in Chinese subjects. Clin Pharmacol Ther 78:370–377.
  • Yin, T., Maekawa, K., Kamide, K., Saito, Y., Hanada, H., Miyashita, K., Kokubo, Y., Akaiwa, Y., Otsubo, R., Nagatsuka, K., Otsuki, T., Horio, T., Takiuchi, S., Kawano, Y., Minematsu, K., Naritomi, H., Tomoike, H., Sawada, J. Miyata, T. (2008). Genetic variations of CYP2C9 in 724 Japanese individuals and their impact on the antihypertensive effects of losartan. Hypertens Res 31:1549–1557.
  • Yokoi, T., Kosaka, Y., Chida, M., Chiba, K., Nakamura, H., Ishizaki, T., Kinoshita, M., Sato, K., Gonzalez, F. J. Kamataki, T. (1996). A new CYP2D6 allele with a nine base insertion in exon 9 in a Japanese population associated with poor metabolizer phenotype. Pharmacogenetics 6:395–401.
  • Yokono, A., Morita, S., Someya, T., Hirokane, G., Okawa, M. Shimoda, K. (2001). The effect of CYP2C19 and CYP2D6 genotypes on the metabolism of clomipramine in Japanese psychiatric patients. J Clin Psychopharmacol 21:549–555.
  • Yokota, H., Tamura, S., Furuya, H., Kimura, S., Watanabe, M., Kanazawa, I., Kondo, I. Gonzalez, F. J. (1993). Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism. Pharmacogenetics 3:256–263.
  • Yokota, M., Inagaki, H., Uematsu, H., Enomoto, N., Goto, J., Sotobata, I. Takahashi, A. (1987). Nonlinear pharmacokinetics of aprindine hydrochloride in oral administration. Arzneimittelforschung 37:184–188.
  • Yonezawa, E., Matsumoto, K., Ueno, K., Tachibana, M., Hashimoto, H., Komamura, K., Kamakura, S., Miyatake, K. Tanaka, K. (2002). Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients. J Clin Pharmacol 42:342–346.
  • Yoshida, R., Nakajima, M., Nishimura, K., Tokudome, S., Kwon, J. T. Yokoi, T. (2003). Effects of polymorphism in promoter region of human CYP2A6 gene (CYP2A6*9) on expression level of messenger ribonucleic acid and enzymatic activity in vivo and in vitro. Clin Pharmacol Ther 74:69–76.
  • Yoshida, R., Nakajima, M., Watanabe, Y., Kwon, J. T. Yokoi, T. (2002). Genetic polymorphisms in human CYP2A6 gene causing impaired nicotine metabolism. Br J Clin Pharmacol 54:511–517.
  • Yoshigae, Y., Konno, K., Takasaki, W. Ikeda, T. (2000). Characterization of UDP-glucuronosyltransferases (UGTS) involved in the metabolism of troglitazone in rats and humans. J Toxicol Sci 25:433–441.
  • Yoshii, K., Kobayashi, K., Tsumuji, M., Tani, M., Shimada, N. Chiba, K. (2000). Identification of human cytochrome P450 isoforms involved in the 7-hydroxylation of chlorpromazine by human liver microsomes. Life Sci 67:175–184.
  • Young, I. M., Leone, R. M., Francis, P., Stovell, P. Silman, R. E. (1985). Melatonin is metabolized to N-acetyl serotonin and 6-hydroxymelatonin in man. J Clin Endocrinol Metab 60:114–119.
  • Young, P. W., Buckle, D. R., Cantello, B. C., Chapman, H., Clapham, J. C., Coyle, P. J., Haigh, D., Hindley, R. M., Holder, J. C., Kallender, H., Latter, A. J., Lawrie, K. W., Mossakowska, D., Murphy, G. J., Roxbee Cox, L., Smith, S. A. (1998). Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor gamma. J Pharmacol Exp Ther 284:751–759.
  • Young, S. D., Britcher, S. F., Tran, L. O., Payne, L. S., Lumma, W. C., Lyle, T. A., Huff, J. R., Anderson, P. S., Olsen, D. B., Carroll, S. S. et al. (1995). L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 39:2602–2605.
  • Yu, A. M., Idle, J. R., Byrd, L. G., Krausz, K. W., Kupfer, A. Gonzalez, F. J. (2003a). Regeneration of serotonin from 5-methoxytryptamine by polymorphic human CYP2D6. Pharmacogenetics 13:173–181.
  • Yu, A. M., Idle, J. R., Herraiz, T., Kupfer, A. Gonzalez, F. J. (2003b). Screening for endogenous substrates reveals that CYP2D6 is a 5-methoxyindolethylamine O-demethylase. Pharmacogenetics 13:307–319.
  • Yu, B. N., Chen, G. L., He, N., Ouyang, D. S., Chen, X. P., Liu, Z. Q. Zhou, H. H. (2003c). Pharmacokinetics of citalopram in relation to genetic polymorphism of CYP2C19. Drug Metab Dispos 31:1255–1259.
  • Yu, K. S., Yim, D. S., Cho, J. Y., Park, S. S., Park, J. Y., Lee, K. H., Jang, I. J., Yi, S. Y., Bae, K. S. Shin, S. G. (2001). Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19. Clin Pharmacol Ther 69:266–273.
  • Yuan, R., Madani, S., Wei, X. X., Reynolds, K. Huang, S. M. (2002). Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. Drug Metab Dispos 30:1311–1319.
  • Yue, Q. Y. Sawe, J. (1997). Different effects of inhibitors on the O- and N-demethylation of codeine in human liver microsomes. Eur J Clin Pharmacol 52:41–47.
  • Yue, Q. Y., Zhong, Z. H., Tybring, G., Dalen, P., Dahl, M. L., Bertilsson, L. Sjoqvist, F. (1998). Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes. Clin Pharmacol Ther 64:384–390.
  • Yumibe, N., Huie, K., Chen, K. J., Clement, R. P. Cayen, M. N. (1995). Identification of human liver cytochrome P450s involved in the microsomal metabolism of the antihistaminic drug loratadine. Int Arch Allergy Immunol 107:420.
  • Yumibe, N., Huie, K., Chen, K. J., Snow, M., Clement, R. P. Cayen, M. N. (1996). Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating antihistamine loratadine. Formation of descarboethoxyloratadine by CYP3A4 and CYP2D6. Biochem Pharmacol 51:165–172.
  • Yun, C. H., Lee, H. S., Lee, H., Rho, J. K., Jeong, H. G. Guengerich, F. P. (1995). Oxidation of the angiotensin II receptor antagonist losartan (DuP 753) in human liver microsomes. Role of cytochrome P4503A(4) in formation of the active metabolite EXP3174. Drug Metab Dispos 23:285–289.
  • Yun, C. H., Shimada, T. Guengerich, F. P. (1991). Purification and characterization of human liver microsomal cytochrome P-450 2A6. Mol Pharmacol 40:679–685.
  • Zaccaro, C., Sweitzer, S., Pipino, S., Gorman, N., Sinclair, P. R., Sinclair, J. F., Nebert, D. W. De Matteis, F. (2001). Role of cytochrome P450 1A2 in bilirubin degradation Studies in Cyp1a2 (-/-) mutant mice. Biochem Pharmacol 61:843–849.
  • Zanger, U. M., Klein, K., Saussele, T., Blievernicht, J., Hofmann, M. H. Schwab, M. (2007). Polymorphic CYP2B6: molecular mechanisms and emerging clinical significance. Pharmacogenomics 8:743–759.
  • Zanger, U. M., Raimundo, S. Eichelbaum, M. (2004). Cytochrome P450 2D6: overview and update on pharmacology, genetics, biochemistry. Naunyn Schmiedebergs Arch Pharmacol 369:23–37.
  • Zaphiropoulos, P. G. (1997). Exon skipping and circular RNA formation in transcripts of the human cytochrome P-450 2C18 gene in epidermis and of the rat androgen binding protein gene in testis. Mol Cell Biol 17:2985–2993.
  • Zeigler-Johnson, C. M., Walker, A. H., Mancke, B., Spangler, E., Jalloh, M., McBride, S., Deitz, A., Malkowicz, S. B., Ofori-Adjei, D., Gueye, S. M. Rebbeck, T. R. (2002). Ethnic differences in the frequency of prostate cancer susceptibility alleles at SRD5A2 and CYP3A4. Hum Hered 54:13–21.
  • Zeldin, D. C., Moomaw, C. R., Jesse, N., Tomer, K. B., Beetham, J., Hammock, B. D. Wu, S. (1996). Biochemical characterization of the human liver cytochrome P450 arachidonic acid epoxygenase pathway. Arch Biochem Biophys 330:87–96.
  • Zgheib, N. K., Frye, R. F., Tracy, T. S., Romkes, M. Branch, R. A. (2006). Validation of incorporating flurbiprofen into the Pittsburgh cocktail. Clin Pharmacol Ther 80:257–263.
  • Zhang, F., Fan, P. W., Liu, X., Shen, L., van Breeman, R. B. Bolton, J. L. (2000). Synthesis and reactivity of a potential carcinogenic metabolite of tamoxifen: 3,4-dihydroxytamoxifen-o-quinone. Chem Res Toxicol 13:53–62.
  • Zhang, J., Tian, Q., Chan, S. Y., Duan, W. Zhou, S. (2005a). Insights into oxazaphosphorine resistance and possible approaches to its circumvention. Drug Resist Updat 8:271–297.
  • Zhang, J., Tian, Q., Yung Chan, S., Chuen Li, S., Zhou, S., Duan, W., Zhu, Y. Z. (2005b). Metabolism and transport of oxazaphosphorines and the clinical implications. Drug Metab Rev 37:611–703.
  • Zhang, J., Tian, Q. Zhou, S. F. (2006a). Clinical pharmacology of cyclophosphamide and ifosfamide. Curr Drug Ther 1:104–168.
  • Zhang, J., Tian, Q., Zhu, Y. Z., Xu, A. L. Zhou, S. F. (2006b). Reversal of resistance to oxazaphosphorines. Curr Cancer Drug Targets 6:385–407.
  • Zhang, K. E., Wu, E., Patick, A. K., Kerr, B., Zorbas, M., Lankford, A., Kobayashi, T., Maeda, Y., Shetty, B. Webber, S. (2001). Circulating metabolites of the human immunodeficiency virus protease inhibitor nelfinavir in humans: structural identification, levels in plasma, and antiviral activities. Antimicrob Agents Chemother 45:1086–1093.
  • Zhang, Q. Y., Kaminsky, L. S., Dunbar, D., Zhang, J. Ding, X. (2007a). Role of small intestinal cytochromes p450 in the bioavailability of oral nifedipine. Drug Metab Dispos 35:1617–1623.
  • Zhang, W. Y., Tu, Y. B., Haining, R. L. Yu, A. M. (2009). Expression and functional analysis of CYP2D6.24, CYP2D6.26, CYP2D6.27, and CYP2D7 isozymes. Drug Metab Dispos 37:1–4.
  • Zhang, X., Chen, Y., Liu, Y., Ren, X., Zhang, Q. Y., Caggana, M. Ding, X. (2003). Single-nucleotide polymorphisms of the human cyp2a13 gene: evidence for a null allele. Drug Metab Dispos 31:1081–1085.
  • Zhang, X., D’Agostino, J., Wu, H., Zhang, Q. Y., von Weymarn, L., Murphy, S. E. Ding, X. (2007b). CYP2A13: variable expression and role in human lung microsomal metabolic activation of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. J Pharmacol Exp Ther 323:570–578.
  • Zhang, X., Su, T., Zhang, Q. Y., Gu, J., Caggana, M., Li, H. Ding, X. (2002). Genetic polymorphisms of the human CYP2A13 gene: identification of single-nucleotide polymorphisms and functional characterization of an Arg257Cys variant. J Pharmacol Exp Ther 302:416–423.
  • Zhang, Y., Zhong, D., Si, D., Guo, Y., Chen, X. Zhou, H. (2005c). Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype. Br J Clin Pharmacol 59:14–17.
  • Zhang, Y. A., Reviriego, J., Lou, Y. Q., Sjoqvist, F. Bertilsson, L. (1990). Diazepam metabolism in native Chinese poor and extensive hydroxylators of S-mephenytoin: interethnic differences in comparison with white subjects. Clin Pharmacol Ther 48:496–502.
  • Zhang, Z., Fasco, M. J., Huang, Z., Guengerich, F. P. Kaminsky, L. S. (1995). Human cytochromes P4501A1 and P4501A2: R-warfarin metabolism as a probe. Drug Metab Dispos 23:1339–1346.
  • Zhang, Z. Y., Fasco, M. J., Huang, L., Guengerich, F. P. Kaminsky, L. S. (1996). Characterization of purified human recombinant cytochrome P4501A1-Ile462 and -Val462: assessment of a role for the rare allele in carcinogenesis. Cancer Res 56:3926–3933.
  • Zhang, Z. Y. Kaminsky, L. S. (1995). Characterization of human cytochromes P450 involved in theophylline 8-hydroxylation. Biochem Pharmacol 50:205–211.
  • Zhao, B., Lee, E. J., Wong, J. Y., Yeoh, P. N. Gong, N. H. (1995). Frequency of mutant CYP1A1, NAT2, and GSTM1 alleles in normal Indians and Malays. Pharmacogenetics 5:275–280.
  • Zhao, F., Loke, C., Rankin, S. C., Guo, J. Y., Lee, H. S., Wu, T. S., Tan, T., Liu, T. C., Lu, W. L., Lim, Y. T., Zhang, Q., Goh, B. C. Lee, S. C. (2004). Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose. Clin Pharmacol Ther 76:210–219.
  • Zharikova, O. L., Ravindran, S., Nanovskaya, T. N., Hill, R. A., Hankins, G. D. Ahmed, M. S. (2007). Kinetics of glyburide metabolism by hepatic and placental microsomes of human and baboon. Biochem Pharmacol 73:2012–2019.
  • Zheng, H., Webber, S., Zeevi, A., Schuetz, E., Zhang, J., Bowman, P., Boyle, G., Law, Y., Miller, S., Lamba, J. Burckart, G. J. (2003). Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 gene polymorphisms. Am J Transplant 3:477–483.
  • Zhong, W. Z. Williams, M. G. (1996). Simultaneous quantitation of pioglitazone and its metabolites in human serum by liquid chromatography and solid phase extraction. J Pharm Biomed Anal 14:465–473.
  • Zhou, D., Afzelius, L., Grimm, S. W., Andersson, T. B., Zauhar, R. J. Zamora, I. (2006). Comparison of methods for the prediction of the metabolic sites for CYP3A4-mediated metabolic reactions. Drug Metab Dispos 34:976–983.
  • Zhou, H., Josephy, P. D., Kim, D. Guengerich, F. P. (2004). Functional characterization of four allelic variants of human cytochrome P450 1A2. Arch Biochem Biophys 422:23–30.
  • Zhou, H. H. Wood, A. J. (1995). Stereoselective disposition of carvedilol is determined by CYP2D6. Clin Pharmacol Ther 57:518–524.
  • Zhou, Q., Yao, T. W., Yu, Y. N. Zeng, S. (2003). Concentration dependent stereoselectivity of propafenone N-depropylation metabolism with human hepatic recombinant CYP1A2. Pharmazie 58:651–653.
  • Zhou, S., Kestell, P. Paxton, J. W. (2002). Predicting pharmacokinetics and drug interactions in patients from in vitro and in vivo models: the experience with 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an anti-cancer drug eliminated mainly by conjugation. Drug Metab Rev 34:751–790.
  • Zhou, S., Paxton, J. W., Tingle, M. D. Kestell, P. (2000). Identification of the human liver cytochrome P450 isoenzyme responsible for the 6-methylhydroxylation of the novel anticancer drug 5,6-dimethylxanthenone-4-acetic acid. Drug Metab Dispos 28:1449–1456.
  • Zhou, S. F. (2008). Drugs behave as substrates, inhibitors, and inducers of human cytochrome P450 3A4. Curr Drug Metab 9:310–322.
  • Zhou, S. F., Di, Y. M., Chan, E., Du, Y. M., Chow, V. D., Xue, C. C., Lai, X., Wang, J. C., Li, C. G., Tian, M. Duan, W. (2008). Clinical pharmacogenetics and potential application in personalized medicine. Curr Drug Metab 9:738–784.
  • Zhu, L. R., Thomas, P. E., Lu, G., Reuhl, K. R., Yang, G. Y., Wang, L. D., Wang, S. L., Yang, C. S., He, X. Y. Hong, J. Y. (2006). CYP2A13 in human respiratory tissues and lung cancers: an immunohistochemical study with a new peptide-specific antibody. Drug Metab Dispos 34:1672–1676.
  • Zhuo, X., Gu, J., Zhang, Q. Y., Spink, D. C., Kaminsky, L. S. Ding, X. (1999). Biotransformation of coumarin by rodent and human cytochromes P-450: metabolic basis of tissue-selective toxicity in olfactory mucosa of rats and mice. J Pharmacol Exp Ther 288:463–471.
  • Zineh, I., Beitelshees, A. L., Gaedigk, A., Walker, J. R., Pauly, D. F., Eberst, K., Leeder, J. S., Phillips, M. S., Gelfand, C. A. Johnson, J. A. (2004). Pharmacokinetics and CYP2D6 genotypes do not predict metoprolol adverse events or efficacy in hypertension. Clin Pharmacol Ther 76:536–544.
  • Zoble, R. G., Kirsten, E. B. Brewington, J. (1989). Pharmacokinetic and pharmacodynamic evaluation of propafenone in patients with ventricular arrhythmia. Propafenone Research Group. Clin Pharmacol Ther 45:535–541.
  • Zourkova, A. Hadasova, E. (2002). Relationship between CYP 2D6 metabolic status and sexual dysfunction in paroxetine treatment. J Sex Marital Ther 28:451–461.
  • Zukunft, J., Lang, T., Richter, T., Hirsch-Ernst, K. I., Nussler, A. K., Klein, K., Schwab, M., Eichelbaum, M. Zanger, U. M. (2005). A natural CYP2B6 TATA box polymorphism (–82T–> C) leading to enhanced transcription and relocation of the transcriptional start site. Mol Pharmacol 67:1772–1782.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.