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Review Article

Structure, function, regulation and polymorphism and the clinical significance of human cytochrome P450 1A2

Shu-Feng ZhouDiscpline of Chinese Medicine, School of Health Sciences, RMIT University, Bundoora, Victoria 3083, AustraliaCorrespondence[email protected]
,
Bo WangDepartment of Pediatrics, Guangdong Women' and Children's Hospital, Guangzhou 510010, China
,
Li-Ping YangDepartment of Pharmacy, Beijing Hospital, Ministry of Health of China, Beijing 100730, China
&
Jun-Ping LiuDepartment of Immunology, Central and Eastern Clinical School, Monash University, Prahran, Victoria 3181, Australia
Pages 268-354 | Received 11 Jun 2009, Accepted 19 Aug 2009, Published online: 04 Dec 2009

References

  • 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.
  • Abbas, R., Chow, C. P., Browder, N. J., Thacker, D., Bramer, S. L., Fu, C. J., et al. (2000). In vitro metabolism and interaction of cilostazol with human hepatic cytochrome P450 isoforms. Hum Exp Toxicol 19:178–184.
  • 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.
  • Aitchison, K. J., Gonzalez, F. J., Quattrochi, L. C., Sapone, A., Zhao, J. H., Zaher, H., et al. (2000a). Identification of novel polymorphisms in the 5’ flanking region of CYP1A2, characterization of interethnic variability, and investigation of their functional significance. Pharmacogenetics 10:695–704.
  • Aitchison, K. J., Jann, M. W., Zhao, J. H., Sakai, T., Zaher, H., Wolff, K., et al. (2000b). Clozapine pharmacokinetics and pharmacodynamics studied with CYP1A2-null mice. J Psychopharmacol 14:353–359.
  • Ajroud-Driss, S., Saeed, M., Khan, H., Siddique, N., Hung, W. Y., Sufit, R., et al. (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., et al. (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.
  • 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.
  • Allorge, D., Chevalier, D., Lo-Guidice, J. M., Cauffiez, C., Suard, F., Baumann, P., et al. (2003). Identification of a novel splice-site mutation in the CYP1A2 gene. Br J Clin Pharmacol 56:341–344.
  • Ambros, V. (2004). The functions of animal microRNAs. Nature 431:350–355.
  • Anderson, G. D., Rosito, G., Mohustsy, M. A., Elmer, G. W. (2003). Drug interaction potential of soy extract and Panax ginseng. J Clin Pharmacol 43:643–648.
  • Andersson, T., Bergstrand, R., Cederberg, C., Eriksson, S., Lagerstrom, P. O., Skanberg, I. (1991). Omeprazole treatment does not affect the metabolism of caffeine. Gastroenterology 101:943–947.
  • 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.
  • Ando, Y., Fuse, E., Figg, W. D. (2002). Thalidomide metabolism by the CYP2C subfamily. Clin Cancer Res 8:1964–1973.
  • Androutsopoulos, V. P., Tsatsakis, A. M., Spandidos, D. A. (2009). Cytochrome P450 CYP1A1: wider roles in cancer progression and prevention. BMC Cancer 9:187.
  • Atherton, K. M., Mutch, E., Ford, D. (2006). Metabolism of the soyabean isoflavone daidzein by CYP1A2 and the extra-hepatic CYPs 1A1 and 1B1 affects biological activity. Biochem Pharmacol 72:624–631.
  • Ayalogu, E. O., Snelling, J., Lewis, D. F., Talwar, S., Clifford, M. N., Ioannides, C. (1995). Induction of hepatic CYP1A2 by the oral administration of caffeine to rats: lack of association with the Ah locus. Biochim Biophys Acta 1272:89–94.
  • Azuma, R., Komuro, M., Korsch, B. H., Andre, J. C., Onnagawa, O., Black, S. R., et al. (1999). Metabolism and disposition of GTS-21, a novel drug for Alzheimer’s disease. Xenobiotica 29:747–762.
  • B’Chir, F., Pavanello, S., Knani, J., Boughattas, S., Arnaud, M. J., Saguem, S. (2009). CYP1A2 genetic polymorphisms and adenocarcinoma lung cancer risk in the Tunisian population. Life Sci 84:779–784.
  • Bachmann, K., White, D., Jauregui, L., Schwartz, J. I., Agrawal, N. G., Mazenko, R., et al. (2003). An evaluation of the dose-dependent inhibition of CYP1A2 by rofecoxib using theophylline as a CYP1A2 probe. J Clin Pharmacol 43:1082–1090.
  • Backlund, M., Weidolf, L., Ingelman-Sundberg, M. (1999). Structural and mechanistic aspects of transcriptional induction of cytochrome P450 1A1 by benzimidazole derivatives in rat hepatoma H4IIE cells. Eur J Biochem 261:66–71.
  • Backman, J. T., Granfors, M. T., Neuvonen, P. J. (2006a). Rifampicin is only a weak inducer of CYP1A2-mediated presystemic and systemic metabolism: studies with tizanidine and caffeine. Eur J Clin Pharmacol 62:451–461.
  • Backman, J. T., Karjalainen, M. J., Neuvonen, M., Laitila, J., Neuvonen, P. J. (2006b). Rofecoxib is a potent inhibitor of cytochrome P4501A2: studies with tizanidine and caffeine in healthy subjects. Br J Clin Pharmacol 62:345–357.
  • Backman, J. T., Schroder, M. T., Neuvonen, P. J. (2008). Effects of gender and moderate smoking on the pharmacokinetics and effects of the CYP1A2 substrate tizanidine. Eur J Clin Pharmacol 64:17–24.
  • Baiocchi, L., Frigerio, A., Giannangeli, M., Palazzo, G. (1974). Basic metabolites of trazodone in humans. Arzneimittelforschung 24:1699–1706.
  • Bapiro, T. E., Andersson, T. B., Otter, C., Hasler, J. A., Masimirembwa, C. M. (2002). Cytochrome P450 1A1/2 induction by antiparasitic drugs: dose-dependent increase in ethoxyresorufin O-deethylase activity and mRNA caused by quinine, primaquine and albendazole in HepG2 cells. Eur J Clin Pharmacol 58:537–542.
  • Barrenetxe, J., Delagrange, P., Martinez, J. A. (2004). Physiological and metabolic functions of melatonin. J Physiol Biochem 60:61–72.
  • Bartel, D. P. (2009). MicroRNAs: target recognition and regulatory functions. Cell 136:215–233.
  • Bartoli, A., Xiaodong, S., Gatti, G., Cipolla, G., Marchiselli, R., Perucca, E. (1996). The influence of ethnic factors and gender on CYP1A2-mediated drug disposition: a comparative study in Caucasian and Chinese subjects using phenacetin as a marker substrate. Ther Drug Monit 18:586–591.
  • Batty, K. T., Davis, T. M., Ilett, K. F., Dusci, L. J., Langton, S. R. (1995). The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects. Br J Clin Pharmacol 39:305–311.
  • Beasley, C. M., Jr., Tollefson, G., Tran, P., Satterlee, W., Sanger, T., Hamilton, S. (1996). Olanzapine versus placebo and haloperidol: acute phase results of the North American double-blind olanzapine trial. Neuropsychopharmacology 14:111–123.
  • Becquemont, L., Ragueneau, I., Le Bot, M. A., Riche, C., Funck-Brentano, C., Jaillon, P. (1997). Influence of the CYP1A2 inhibitor fluvoxamine ontacrine pharmacokinetics in humans. Clin Pharmacol Ther 61:619–627.
  • Bensimon, G., Lacomblez, L., Meininger, V. (1994). A controlled trial of riluzole in amyotrophic lateral sclerosis. ALS/Riluzole Study Group. N EnglJMed 330:585–591.
  • Berecz, R., de la Rubia A., Dorado, P., Fernandez-Salguero, P., Dahl, M.L., Llerena, A. (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.
  • Berger, W., De Chandt, M. T., Cairns, C. B. (2007). Zileuton: clinical implications of 5-lipoxygenase inhibition in severe airway disease. Int J Clin Pract 61:663–676.
  • Berthou, F., Guillois, B., Riche, C., Dreano, Y., Jacqz-Aigrain, E., Beaune, P. H. (1992). Interspecies variations in caffeine metabolism related to cytochrome P4501A enzymes. Xenobiotica 22:671–680.
  • Bertilsson, L., Carrillo, J. A., Dahl, M. L., Llerena, A., Alm, C., Bondesson, U., et al. (1994). Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br J Clin Pharmacol 38:471–473.
  • Bilgen, T., Tosun, O., Luleci, G., Keser, I. (2008). Frequencies of four genetic polymorphisms in the CYP1A2 gene in Turkish population. Genetika 44:1133–1136.
  • 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.
  • Boberg, E. W., Miller, E. C., Miller, J. A. (1986). The metabolic sulfonation and side-chain oxidation of 3’-hydroxyisosafrole in the mouse and its inactivity as a hepatocarcinogen relative to 1’-hydroxysafrole. Chem Biol Interact 59:73–97.
  • Boberg, E. W., Miller, E. C., Miller, J. A., Poland, A., Liem, A. (1983). Strong evidence from studies with brachymorphic mice and pentachlorophenol that 1’-sulfooxysafrole is the major ultimate electrophilic and carcinogenic metabolite of 1’-hydroxysafrole in mouse liver. Cancer Res 43:5163–5173.
  • Bock, K. W., Schrenk, D., Forster, A., Griese, E. U., Morike, K., Brockmeier, D., et al. (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., Grabnar, I., Rozman, B., Logar, D., Tomsic, M., Suput, D., et al. (2009). Investigation of the influence of CYP1A2 and CYP2C19 genetic polymorphism on A771726 pharmacokinetics in leflunomide treated patients with rheumatoid arthritis. Drug Metab Dispos 37:2061–2068.
  • 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., et al. (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.
  • Borchert, P., Wislocki, P. G., Miller, J. A., Miller, E. C. (1973). The metabolism of the naturally occurring hepatocarcinogen safrole to 1’-hydroxysafrole and the electrophilic reactivity of 1’-acetoxysafrole. Cancer Res 33:575–589.
  • 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.
  • Botto, F., Seree, E., el Khyari S., de Sousa, G., Massacrier, A., Placidi, M., et al. (1994). Tissue-specific expression and methylation of the human CYP2E1 gene. Biochem Pharmacol 48:1095–1103.
  • 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.
  • Breinholt, V. M., Rasmussen, S. E., Brosen, K., Friedberg, T. H. (2003). In vitro metabolism of genistein and tangeretin by human and murine cytochrome P450s. Pharmacol Toxicol 93:14–22.
  • Brosen, K. (1995). Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet 29(Suppl 1):20–25.
  • Brouwers, E. E., Sohne, M., Kuipers, S., van Gorp E. C., Schellens, J. H., Koks, C. H., et al. (2009). Ciprofloxacin strongly inhibits clozapine metabolism: two case reports. Clin Drug Investig 29:59–63.
  • Bruno, R., Vivier, N., Montay, G., Le Liboux, A., Powe, L. K., Delumeau, J. C., et al. (1997). Population pharmacokinetics of riluzole in patients with amyotrophic lateral sclerosis. Clin Pharmacol Ther 62:518–526.
  • 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.
  • Bulger, W. H., Kupfer, D. (1989). Characteristics of monooxygenase-mediated covalent binding of methoxychlor in human and rat liver microsomes. Drug Metab Dispos 17:487–494.
  • Bulger, W. H., Muccitelli, R. M., Kupfer, D. (1978). Studies on the in vivo and in vitro estrogenic activities of methoxychlor and its metabolites. Role of hepatic mono-oxygenase in methoxychlor activation. Biochem Pharmacol 27:2417–2423.
  • Burke, M. D., Thompson, S., Weaver, R. J., Wolf, C. R., Mayer, R. T. (1994). Cytochrome P450 specificities of alkoxyresorufin O-dealkylation in human and rat liver. Biochem Pharmacol 48:923–936.
  • Burton, J., Ijjaali, I., Barberan, O., Petitet, F., Vercauteren, D. P., Michel, A. (2006). Recursive partitioning for the prediction of cytochromes P450 2D6 and 1A2 inhibition: importance of the quality of the dataset. J Med Chem 49:6231–6240.
  • Buters, J. T., Shou, M., Hardwick, J. P., Korzekwa, K. R., Gonzalez, F. J. (1995). cDNA-directed expression of human cytochrome P450 CYP1A1 using baculovirus. Purification, dependency on NADPH-P450 oxidoreductase, and reconstitution of catalytic properties without purification. Drug Metab Dispos 23:696–701.
  • Buters, J. T., Tang, B. K., Pineau, T., Gelboin, H. V., Kimura, S., Gonzalez, F. J. (1996). Role of CYP1A2 in caffeine pharmacokinetics and metabolism: studies using mice deficient in CYP1A2. Pharmacogenetics 6:291–296.
  • Butler, M. A., Lang, N. P., Young, J. F., Caporaso, N. E., Vineis, P., Hayes, R. B., et al. (1992). Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 2:116–127.
  • Byerly, M. J., DeVane, C. L. (1996). Pharmacokinetics of clozapine and risperidone: a review of recent literature. JClin Psychopharmacol 16:177–187.
  • 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) P450 inhuman liver microsomes. Drug Metab Dispos 15:237–249.
  • Carrillo, J. A., Christensen, M., Ramos, S. I., Alm, C., Dahl, M. L., Benitez, J., et al. (2000). Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine. Ther Drug Monit 22:409–417.
  • 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.
  • Carthew, R. W., Sontheimer, E. J. (2009). Origins and mechanisms of miRNAs and siRNAs. Cell 136:642–655.
  • Carver, L. A., Jackiw, V., Bradfield, C. A. (1994). The 90-kDa heat shock protein is essential for Ah receptor signaling in a yeast expression system. J Biol Chem 269:30109–30112.
  • Carver, L. A., LaPres, J. J., Jain, S., Dunham, E. E., Bradfield, C. A. (1998). Characterization of the Ah receptor-associated protein, ARA9. J Biol Chem 273:33580–33587.
  • 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.
  • Chan, V., Charles, B. G., Tett, S. E. (2005). Population pharmacokinetics and association between A771726 plasma concentrations and disease activity measures following administration of leflunomide to people with rheumatoid arthritis. Br J Clin Pharmacol 60:257–264.
  • Chang, T. K., Chen, J., Lee, W. B. (2001). Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism-based inactivation of CYP1A2. J Pharmacol Exp Ther 299:874–882.
  • Chang, T. K., Waxman, D. J. (2006). Enzymatic analysis of cDNA-expressed human CYP1A1, CYP1A2, and CYP1B1 with 7-ethoxyresorufin as substrate. Methods Mol Biol 320:85–90.
  • Chang, W. H., Lin, S. K., Lane, H. Y., Hu, W. H., Jann, M. W., Lin, H. N. (1997). Clozapine dosages and plasma drug concentrations. J Formos Med Assoc 96:599–605.
  • Chen, C., Meng, L., Ma, X., Krausz, K. W., Pommier, Y., Idle, J. R., et al. (2006a). Urinary metabolite profiling reveals CYP1A2-mediated metabolism of NSC686288 (aminoflavone). J Pharmacol Exp Ther 318:1330–1342.
  • Chen, C. D., Doray, B., Kemper, B. (1998). A conserved proline-rich sequence between the N-terminal signal-anchor and catalytic domains is required for assembly of functional cytochrome P450 2C2. Arch Biochem Biophys 350:233–238.
  • Chen, H., Howald, W. N., Juchau, M. R. (2000). Biosynthesis of all-trans-retinoic acid from all-trans-retinol: catalysis of all-trans-retinol oxidation by human P450 cytochromes. Drug Metab Dispos 28:315–322.
  • Chen, S., Zhou, D. (1992). Functional domains of aromatase cytochrome P450 inferred from comparative analyses of amino acid sequences and substantiated by site-directed mutagenesis experiments. J Biol Chem 267:22587–22594.
  • Chen, X., Wang, H., Xie, W., Liang, R., Wei, Z., Zhi, L., et al. (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., et al. (2005). The G-3113A polymorphism in CYP1A2 affects the caffeine metabolic ratio in a Chinese population. Clin Pharmacol Ther 78:249–259.
  • Chen, Y., Xiao, P., Ou-Yang, D. S., Fan, L., Guo, D., Wang, Y. N., et al. (2009). Simultaneous action of the flavonoid quercetin on cytochrome P450 (CYP) 1A2, CYP2A6, N-acetyltransferase and xanthine oxidase activity in healthy volunteers. Clin Exp Pharmacol Physiol 36:828–833.
  • Cheung, C., Ma, X., Krausz, K. W., Kimura, S., Feigenbaum, L., Dalton, T. P., et al. (2005). Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in mice humanized for CYP1A1 and CYP1A2. Chem Res Toxicol 18:1471–1478.
  • Cheung, Y. L., Snelling, J., Mohammed, N. N., Gray, T. J., Ioannides, C. (1996). Interaction with the aromatic hydrocarbon receptor, CYP1A induction, and mutagenicity of a series of diaminotoluenes: implications for their carcinogenicity. Toxicol Appl Pharmacol 139:203–211.
  • Chevalier, D., Cauffiez, C., Allorge, D., Lo-Guidice, J. M., Lhermitte, M., Lafitte, J. J., et al. (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., Yokoi, T., Fukui, T., Kinoshita, M., Yokota, J., Kamataki, T. (1999). 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.
  • Cho, U. S., Park, E. Y., Dong, M. S., Park, B. S., Kim, K., Kim, K. H. (2003). Tight-binding inhibition by α-naphthoflavone of human cytochrome P450 1A2. Biochim Biophys Acta 1648:195–202.
  • Chohan, K. K., Paine, S. W., Mistry, J., Barton, P., Davis, A. M. (2005). A rapid computational filter for cytochrome P450 1A2 inhibition potential of compound libraries. J Med Chem 48:5154–5161.
  • Choudhary, D., Jansson, I., Stoilov, I., Sarfarazi, M., Schenkman, J. B. (2004). Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1. Drug Metab Dispos 32:840–847.
  • Christiansen, L., Bygum, A., Jensen, A., Thomsen, K., Brandrup, F., Horder, M., et al. (2000). Association between CYP1A2 polymorphism and susceptibility to porphyria cutanea tarda. Hum Genet 107:612–614.
  • Chun, Y. J., Kim, M. Y., Guengerich, F. P. (1999). Resveratrol is a selective human cytochrome P450 1A1 inhibitor. Biochem Biophys Res Commun 262:20–24.
  • Chun, Y. J., Ryu, S. Y., Jeong, T. C., Kim, M. Y. (2001). Mechanism-based inhibition of human cytochrome P450 1A1 by rhapontigenin. Drug Metab Dispos 29:389–393.
  • Chung, W. G., Park, C. S., Roh, H. K., Lee, W. K., Cha, Y. N. (2000). Oxidation of ranitidine by isozymes of flavin-containing monooxygenase and cytochrome P450. Jpn J Pharmacol 84:213–220.
  • Clarke, S. E., Ayrton, A. D., Chenery, R. J. (1994). Characterization of the inhibition of P4501A2 by furafylline. Xenobiotica 24:517–526.
  • Coller, J. K., Somogyi, A. A., Bochner, F. (1999). Comparison of S-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol 48:158–167.
  • Corchero, J., Pimprale, S., Kimura, S., Gonzalez, F. J. (2001). 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.
  • 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.
  • Cummings, A. M. (1997). Methoxychlor as a model for environmental estrogens. Crit Rev Toxicol 27:367–379.
  • Curi-Pedrosa, R., Daujat, M., Pichard, L., Ourlin, J. C., Clair, P., Gervot, L., et al. (1994). Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture. J Pharmacol Exp Ther 269:384–392.
  • Cvrk, T., Strobel, H. W. (1998). Photoaffinity labeling of cytochrome P4501A1 with azidocumene: identification of cumene hydroperoxide binding region. Arch Biochem Biophys 349:95–104.
  • Dai, R., Zhai, S., Wei, X., Pincus, M. R., Vestal, R. E., Friedman, F. K. (1998). Inhibition of human cytochrome P450 1A2 by flavone: a molecular modeling study. J Protein Chem 17:643–650.
  • Dandara, C., Basvi, P. T., Bapiro, T. E., Sayi, J., Hasler, J. A. (2004). Frequency of – 163 C>A and 63 C>G single nucleotide polymorphism of cytochrome P450 1A2 in two African populations. Clin Chem Lab Med 42:939–941.
  • De Rienzo F., Fanelli, F., Menziani, M. C., De Benedetti P. G. (2000). Theoretical investigation of substrate specificity for cytochromes P450 IA2, P450 IID6 and P450 IIIA4. J Comput Aided Mol Des 14:93–116.
  • Denison, M. S., Nagy, S. R. (2003). Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43:309–334.
  • Desta, Z., Kerbusch, T., Soukhova, N., Richard, E., Ko, J. W., Flockhart, D. A. (1998). Identification and characterization of human cytochrome P450 isoforms interacting with pimozide. J Pharmacol Exp Ther 285:428–437.
  • Desta, Z., Soukhova, N., Mahal, S. K., Flockhart, D. A. (2000). Interaction of cisapride with the human cytochrome P450 system: metabolism and inhibition studies. Drug Metab Dispos 28:789–800.
  • 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., Wu, G. M., Morocho, A. M., Flockhart, D. A. (2002). The gastroprokinetic and antiemetic drug metoclopramide is a substrate and inhibitor of cytochrome P450 2D6. Drug Metab Dispos 30:336–343.
  • 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 inter-individual variation in phenacetin disposition. Br J Clin Pharmacol 16:157–166.
  • Di Consiglio, E., Meneguz, A., Testai, E. (2005). Organo-phosphorothionate pesticides inhibit the bioactivation of imipramine by human hepatic cytochrome P450s. Toxicol Appl Pharmacol 205:237–246.
  • Diaz, D., Fabre, I., Daujat, M., Saint Aubert B., Bories, P., Michel, H., et al. (1990). Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology 99:737–747.
  • Dilger, K., Zheng, Z., Klotz, U. (1999). Lack of drug interaction between omeprazole, lansoprazole, pantoprazole and theophylline. Br J Clin Pharmacol 48:438–444.
  • Dixon, C. M., Colthup, P. V., Serabjit-Singh, C. J., Kerr, B. M., Boehlert, C. C., Park, G. R., et al. (1995). Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. Drug Metab Dispos 23:1225–1230.
  • Djordjevic, N., Ghotbi, R., Bertilsson, L., Jankovic, S., Aklillu, E. (2008). Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes. Eur J Clin Pharmacol 64:381–385.
  • Dockrell, D. H., Kinghorn, G. R. (2001). Imiquimod and resiquimod as novel immunomodulators. J Antimicrob Chemother 48:751–755.
  • Dolwick, K. M., Schmidt, J. V., Carver, L. A., Swanson, H. I., Bradfield, C. A. (1993). Cloning and expression of a human Ah receptor cDNA. Mol Pharmacol 44:911–917.
  • Dorado, P., Berecz, R., Penas-Lledo, E. M., de laRubia, 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.
  • Doude van Troostwijk L. J., Koopmans, R. P., Vermeulen, H. D., Guchelaar, H. J. (2003). CYP1A2 activity is an important determinant of clozapine dosage in schizophrenic patients. Eur J Pharm Sci 20:451–457.
  • Dragin, N., Dalton, T. P., Miller, M. L., Shertzer, H. G., Nebert, D. W. (2006). For dioxin-induced birth defects, mouse or human CYP1A2 in maternal liver protects whereas mouse CYP1A1 and CYP1B1 are inconsequential. J Biol Chem 281:18591–18600.
  • Dragin, N., Shi, Z., Madan, R., Karp, C. L., Sartor, M. A., Chen, C., et al. (2008). Phenotype of the Cyp1a1/1a2/1b1−/− triple-knockout mouse. Mol Pharmacol 73:1844–1856.
  • Dzeletovic, N., McGuire, J., Daujat, M., Tholander, J., Ema, M., Fujii-Kuriyama, Y., et al. (1997). Regulation of dioxin receptor function by omeprazole. J Biol Chem 272:12705–12713.
  • Eagling, V. A., Tjia, J. F., Back, D. J. (1998). Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br J Clin Pharmacol 45:107–114.
  • Eap, C. B., Bender, S., Jaquenoud Sirot E., Cucchia, G., Jonzier-Perey, M., Baumann, P., et al. (2004). Nonresponse to clozapine and ultrarapid CYP1A2 activity: clinical data and analysis of CYP1A2 gene. J Clin Psychopharmacol 24:214–219.
  • Echizen, H., Tanizaki, M., Tatsuno, J., Chiba, K., Berwick, T., Tani, M., et al. (2000). Identification of CYP3A4 as the enzyme involved in the mono-N-dealkylation of disopyramide enantiomers in humans. Drug Metab Dispos 28:937–944.
  • Edwards, R. J., Price, R. J., Watts, P. S., Renwick, A. B., Tredger, J. M., Boobis, A. R., et al. (2003). Induction of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos 31:282–288.
  • Elkis, H. (2007). Treatment-resistant schizophrenia. Psychiatr Clin North Am 30:511–533.
  • Ema, M., Ohe, N., Suzuki, M., Mimura, J., Sogawa, K., Ikawa, S., et al. (1994). Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors. J Biol Chem 269:27337–27343.
  • Engel, G., Hofmann, U., Heidemann, H., Cosme, J., Eichelbaum, M. (1996). Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation. Clin Pharmacol Ther 59:613–623.
  • Evans, B. R., Karchner, S. I., Allan, L. L., Pollenz, R. S., Tanguay, R. L., Jenny, M. J., et al. (2008). Repression of aryl hydrocarbon receptor (AhR) signaling by AhR repressor: role of DNA binding and competition for AhR nuclear translocator. Mol Pharmacol 73:387–398.
  • Faber, M. S., Fuhr, U. (2004). Time response of cytochrome P450 1A2 activity on cessation of heavy smoking. Clin Pharmacol Ther 76:178–184.
  • Faber, M. S., Jetter, A., Fuhr, U. (2005). Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol 97:125–134.
  • 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.
  • 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.
  • Fenton, M., Rathbone, J., Reilly, J., Sultana, A. (2007). Thioridazine for schizophrenia. Cochrane Database Syst Rev:CD001944.
  • Fisone, G., Borgkvist, A., Usiello, A. (2004). Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci 61:857–872.
  • Fontaine, F., Delescluse, C., de Sousa, G., Lesca, P., Rahmani, R. (1999). Cytochrome 1A1 induction by primaquine in human hepatocytes and HepG2 cells: absence of binding to the aryl hydrocarbon receptor. Biochem Pharmacol 57:255–262.
  • Fontana, R. J., Lown, K. S., Paine, M. F., Fortlage, L., Santella, R. M., Felton, J. S., et al. (1999). Effects of a chargrilled meat diet on expression of CYP3A, CYP1A, and P-glycoprotein levels in healthy volunteers. Gastroenterology 117:89–98.
  • Frye, R. F., Matzke, G. R., Adedoyin, A., Porter, J. A., Branch, R. A. (1997). Validation of the five-drug “Pittsburgh cocktail” approach for assessment of selective regulation of drug-metabolizing enzymes. Clin Pharmacol Ther 62:365–376.
  • 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.
  • Fuhr, U., Muller-Peltzer, H., Kern, R., Lopez-Rojas, P., Junemann, M., Harder, S., et al. (2002). Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 58:45–53.
  • Fuhr, U., Strobl, G., Manaut, F., Anders, E. M., Sorgel, F., Lopez-de-Brinas, E., et al. (1993). Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isoform CYP1A2. Mol Pharmacol 43:191–199.
  • Fujisawa-Sehara, A., Sogawa, K., Yamane, M., Fujii-Kuriyama, Y. (1987). Characterization of xenobiotic responsive elements upstream from the drug-metabolizing cytochrome P450C gene: a similarity to glucocorticoid regulatory elements. Nucleic Acids Res 15:4179–4191.
  • Fukami, T., Nakajima, M., Sakai, H., Katoh, M., Yokoi, T. (2007). CYP2A13 metabolizes the substrates of human CYP1A2, phenacetin, and theophylline. Drug Metab Dispos 35:335–339.
  • Furuya, H., Shimizu, T., Hatano, M., Fujii-Kuriyama, Y. (1989a). Mutations at the distal and proximal sites of cytochrome P450d changed regio-specificity of acetanilide hydroxylations. Biochem Biophys Res Commun 160:669–676.
  • Furuya, H., Shimizu, T., Hirano, K., Hatano, M., Fujii-Kuriyama, Y., Raag, R., et al. (1989b). Site-directed mutageneses of rat liver cytochrome P450d: catalytic activities toward benzphetamine and 7-ethoxycoumarin. Biochemistry 28:6848–6857.
  • Ganesan, S., Tekwani, B. L., Sahu, R., Tripathi, L. M., Walker, L. A. (2009). Cytochrome P(450) — Dependent toxic effects of primaquine on human erythrocytes. Toxicol Appl Pharmacol [Epub ahead of print]
  • Gantenbein, M., Attolini, L., Bruguerolle, B., Villard, P. H., Puyoou, F., Durand, A., et al. (2000). Oxidative metabolism of bupivacaine into pipecolylxylidine in humans is mainly catalyzed by CYP3A. Drug Metab Dispos 28:383–385.
  • Gerbal-Chaloin, S., Pichard-Garcia, L., Fabre, J. M., Sa-Cunha, A., Poellinger, L., Maurel, P., et al. (2006). Role of CYP3A4 in the regulation of the aryl hydrocarbon receptor by omeprazole sulphide. Cell Signal 18:740–750.
  • Gerber, N. C., Sligar, S. G. (1994). A role for Asp-251 in cytochrome P450cam oxygen activation. J Biol Chem 269:4260–4266.
  • 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.
  • Ghotbi, R., Gomez, A., Milani, L., Tybring, G., Syvanen, A. C., Bertilsson, L., et al. (2009). Allele-specific expression and gene methylation in the control of CYP1A2 mRNA level in human livers. Pharmacogenomics J 9:208–217.
  • Gjertsen, F. B., Solheim, E., Scheline, R. R. (1988). Metabolism of aromatic plant ketones in rats: acetovanillone and paeonol. Xenobiotica 18:225–234.
  • Glatt, H. (1997). Sulfation and sulfotransferases 4: bioactivation of mutagens via sulfation. FASEB J 11:314–321.
  • Gleeson, M. P. (2008). Generation of a set of simple, interpretable ADMET rules of thumb. J Med Chem 51:817–834.
  • Goda, R., Nagai, D., Akiyama, Y., Nishikawa, K., Ikemoto, I., Aizawa, Y., et al. (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.
  • Gooderham, N. J., Murray, S., Lynch, A. M., Yadollahi-Farsani, M., Zhao, K., Rich, K., et al. (1997). Assessing human risk to heterocyclic amines. Mutat Res 376:53–60.
  • 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.
  • Granfors, M. T., Backman, J. T., Laitila, J., Neuvonen, P. J. (2004a). Tizanidine is mainly metabolized by cytochrome P450 1A2 in vitro. Br J Clin Pharmacol 57:349–353.
  • Granfors, M. T., Backman, J. T., Laitila, J., Neuvonen, P. J. (2005). Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2. Clin Pharmacol Ther 78:400–411.
  • Granfors, M. T., Backman, J. T., Neuvonen, M., Ahonen, J., Neuvonen, P. J. (2004b). Fluvoxamine drastically increases concentrations and effects of tizanidine: a potentially hazardous interaction. Clin Pharmacol Ther 75:331–341.
  • Granfors, M. T., Backman, J. T., Neuvonen, M., Neuvonen, P. J. (2004c). Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism. Clin Pharmacol Ther 76:598–606.
  • Granneman, G. R., Karol, M. D., Locke, C. S., Cavanaugh, J. H. (1995). Pharmacokinetic interaction between lansoprazole and theophylline. Ther Drug Monit 17:460–464.
  • Gristwood, R. W., Greaves, J. L. (1999). Levobupivacaine: a new safer long acting local anaesthetic agent. Expert Opin Investig Drugs 8:861–876.
  • 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.
  • Gschwind, H. P., Pfaar, U., Waldmeier, F., Zollinger, M., Sayer, C., Zbinden, P., et al. (2005). Metabolism and disposition of imatinib mesylate in healthy volunteers. Drug Metab Dispos 33:1503–1512.
  • 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.
  • Guitton, J., Buronfosse, T., Desage, M., Flinois, J. P., Perdrix, J. P., Brazier, J. L., et al. (1998). Possible involvement of multiple human cytochrome P450 isoforms in the liver metabolism of propofol. Br J Anaesth 80:788–795.
  • 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.
  • Gunes, A., Ozbey, G., Vural, E. H., Uluoglu, C., Scordo, M. G., Zengil, H., et al. (2009). Influence of genetic polymorphisms, smoking, gender and age on CYP1A2 activity in a Turkish population. Pharmacogenomics 10:769–778.
  • Gurley, B. J., Gardner, S. F., Hubbard, M. A., Williams, D. K., Gentry, W. B., Cui, Y., et al. (2005). Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John’s wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging 22:525–539.
  • 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.
  • Ha, H. R., Chen, J., Krahenbuhl, S., Follath, F. (1996). Biotransformation of caffeine by cDNA-expressed human cytochromes P-450. Eur J Clin Pharmacol 49:309–315.
  • Haarmann-Stemmann, T., Abel, J. (2006). The arylhydrocarbon receptor repressor (AhRR): structure, expression, and function. Biol Chem 387:1195–1199.
  • Haarmann-Stemmann, T., Bothe, H., Kohli, A., Sydlik, U., Abel, J., Fritsche, E. (2007). Analysis of the transcriptional regulation and molecular function of the aryl hydrocarbon receptor repressor in human cell lines. Drug Metab Dispos 35:2262–2269.
  • Hadjokas, N. E., Dai, R., Friedman, F. K., Spence, M. J., Cusack, B. J., Vestal, R. E., et al. (2002). Arginine to lysine 108 substitution in recombinant CYP1A2 abolishes methoxyresorufin metabolism in lymphoblastoid cells. Br J Pharmacol 136:347–352.
  • Hamdy, S. I., Hiratsuka, M., Narahara, K., Endo, N., El-Enany, M., Moursi, N., et al. (2003). Genotyping of four genetic polymorphisms in the CYP1A2 gene in the Egyptian population. Br J Clin Pharmacol 55:321–324.
  • Hammons, G. J., Yan-Sanders, Y., Jin, B., Blann, E., Kadlubar, F. F., Lyn-Cook, B. D. (2001). Specific site methylation in the 5’-flanking region of CYP1A2 interindividual differences in human livers. Life Sci 69:839–845.
  • Han, X. M., Chen, X. P., Wu, Q. N., Jiang, C. H., Zhou, H. H. (2000). G-2964A and C734A genetic polymorphisms of CYP1A2 in Chinese population. Acta Pharmacol Sin 21:1031–1034.
  • Han, X. M., Ou-Yang, D. S., Lu, P. X., Jiang, C. H., Shu, Y., Chen, X. P., et al. (2001). Plasma caffeine metabolite ratio (17X/137X) in vivo associated with G-2964A and C734A polymorphisms of human CYP1A2. Pharmacogenetics 11:429–435.
  • Han, X. M., Ouyang, D. S., Chen, X. P., Shu, Y., Jiang, C. H., Tan, Z. R., et al. (2002). Inducibility of CYP1A2 by omeprazole in vivo related to the genetic polymorphism of CYP1A2. Br J Clin Pharmacol 54:540–543.
  • 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.
  • 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.
  • Harrison, L. I., Skinner, S. L., Marbury, T. C., Owens, M. L., Kurup, S., McKane, S., et al. (2004). Pharmacokinetics and safety of imiquimod 5% cream in the treatment of actinic keratoses of the face, scalp, or hands and arms. Arch Dermatol Res 296:6–11.
  • Harstad, E. B., Guite, C. A., Thomae, T. L., Bradfield, C. A. (2006). Liver deformation in Ahr-null mice: evidence for aberrant hepatic perfusion in early development. Mol Pharmacol 69:1534–1541.
  • Hartmann, M., Zech, K., Bliesath, H., Steinijans, V. W., Koch, H., Wurst, W., et al. (1999). Pantoprazole lacks induction of CYP1A2 activity in man. Int J Clin Pharmacol Ther 37:159–164.
  • Hartter, S., Korhonen, T., Lundgren, S., Rane, A., Tolonen, A., Turpeinen, M., et al. (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. PharmRes 19:1034–1037.
  • 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.
  • Haslemo, T., Eikeseth, P. H., Tanum, L., Molden, E., Refsum, H. (2006). The effect of variable cigarette consumption on the interaction with clozapine and olanzapine. Eur J Clin Pharmacol 62:1049–1053.
  • He, L., Hannon, G. J. (2004). MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531.
  • 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.
  • Higdon, J. V., Frei, B. (2006). Coffee and health: a review of recent human research. Crit Rev Food Sci Nutr 46:101–123.
  • 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.
  • Hirota, T., Ieiri, I., Takane, H., Maegawa, S., Hosokawa, M., Kobayashi, K., et al. (2004). Allelic expression imbalance of the human CYP3A4 gene and individual phenotypic status. Hum Mol Genet 13:2959–2969.
  • Hiroya, K., Ishigooka, M., Shimizu, T., Hatano, M. (1992). Role of Glu318 and Thr319 in the catalytic function of cytochrome P450d (P4501A2): effects of mutations on the methanol hydroxylation. FASEB J 6:749–751.
  • Hiroya, K., Murakami, Y., Shimizu, T., Hatano, M., Ortiz de Montellano, P. R. (1994). Differential roles of Glu318 and Thr319 in cytochrome P450 1A2 catalysis supported by NADPH-cytochrome P450 reductase and tert-butyl hydroperoxide. Arch Biochem Biophys 310:397–401.
  • Hockley, S. L., Arlt, V. M., Brewer, D., Giddings, I., Phillips, D. H. (2006). Time- and concentration-dependent changes in gene expression induced by benzo[a]pyrene in two human cell lines, MCF-7 and HepG2. BMC Genomics 7:260.
  • Hollingshead, B. D., Patel, R. D., Perdew, G. H. (2006). Endogenous hepatic expression of the hepatitis B virus X-associated protein 2 is adequate for maximal association with aryl hydrocarbon receptor-90-kDa heat shock protein complexes. Mol Pharmacol 70:2096–2107.
  • Hooper, W. D., Pool, W. F., Woolf, T. F., Gal, J. (1994). Stereoselective hydroxylation of tacrine in rats and humans. Drug Metab Dispos 22:719–724.
  • Hosoya, T., Harada, N., Mimura, J., Motohashi, H., Takahashi, S., Nakajima, O., et al. (2008). Inducibility of cytochrome P450 1A1 and chemical carcinogenesis by benzo[a]pyrene in AhR repressor-deficient mice. Biochem Biophys Res Commun 365:562–567.
  • Hu, M., Krausz, K., Chen, J., Ge, X., Li, J., Gelboin, H. L., et al. (2003). Identification of CYP1A2 as the main isoform for the Phase I hydroxylated metabolism of genistein and aprodrug converting enzyme of methylated isoflavones. Drug Metab Dispos 31:924–931.
  • Huang, J. D., Guo, W. C., Lai, M. D., Guo, Y. L., Lambert, G. H. (1999). Detection of a novel cytochrome P450 1A2 polymorphism (F21L) in Chinese. Drug Metab Dispos 27:98–101.
  • Hughes, A. N., O’Brien, M. E., Petty, W. J., Chick, J. B., Rankin, E., Woll, P. J., et al. (2009). Overcoming CYP1A1/1A2 mediated induction of metabolism by escalating erlotinib dose in current smokers. J Clin Oncol 27:1220–1226.
  • Ikeda, K., Yoshisue, K., Matsushima, E., Nagayama, S., Kobayashi, K., Tyson, C. A., et al. (2000). Bioactivation of tegafurto 5-fluorouracil is catalyzed by cytochrome P450 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 P450 1A2 phenotype are unlikely to be associated with peripheral arterial disease. Clin Pharmacol Ther 54:317–322.
  • 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.
  • Iori, F., da Fonseca, R., Ramos, M. J., Menziani, M. C. (2005). Theoretical quantitative structure-activity relationships of flavone ligands interacting with cytochrome P450 1A1 and 1A2 isozymes. Bioorg Med Chem 13:4366–4374.
  • Ishida, H., Takamatsu, M., Tsuji, K., Kosuge, T. (1987). Studies on active substances in herbs used for oketsu (“stagnant blood”) in Chinese medicine. V. On the anticoagulative principle in moutan cortex. Chem Pharm Bull (Tokyo) 35:846–848.
  • Ishida, K., Taguchi, M., Akao, T., Hashimoto, Y. (2009). Involvement of the CYP1A subfamily in stereoselective metabolism of carvedilol in β-naphthoflavone-treated Caco-2 cells. Biol Pharm Bull 32:513–516.
  • Ishida, M., Otani, K., Kaneko, S., Ohkubo, T., Osanai, T., Yasui, N., et al. (1995). Effects of various factors on steady state plasma concentrations of trazodone and its active metabolite m-chlorophenylpiperazine. Int Clin Psychopharmacol 10:143–146.
  • Ishigooka, M., Shimizu, T., Hiroya, K., Hatano, M. (1992). Role of Glu318 at the putative distal site in the catalytic function of cytochrome P450d. Biochemistry 31:1528–1531.
  • Iwasaki, M., Yoshimura, Y., Asahi, S., Saito, K., Sakai, S., Morita, S., et al. (2004). Functional characterization of single nucleotide polymorphisms with amino acid substitution in CYP1A2, CYP2A6, and CYP2B6 found in the Japanese population. Drug Metab Pharmacokinet 19:444–452.
  • 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.
  • Jann, M. W., Grimsley, S. R., Gray, E. C., Chang, W. H. (1993). Pharmacokinetics and pharmacodynamics of clozapine. Clin Pharmacokinet 24:161–176.
  • Jaquenoud Sirot E., Knezevic, B., Morena, G. P., Harenberg, S., Oneda, B., Crettol, S., et al. (2009). ABCB1 and cytochrome P450 polymorphisms: clinical pharmacogenetics of clozapine. J Clin Psychopharmacol 29:319–326.
  • Jensen, K. G., Dalgaard, L. (1999). In vitro metabolism of the M1-muscarinic agonist 5-(2-ethyl-2H-tetrazol-5-yl)-1-methyl-1,2,3,6-tetrahydropyridine by human hepatic cytochromes P-450 determined at pH 7.4 and 8.5. Drug Metab Dispos 27:125–132.
  • Jensen, K. G., Poulsen, H. E., Doehmer, J., Loft, S. (1995). Kinetics and inhibition by fluvoxamine of phenacetin O-deethylation in V79 cells expressing human CYP1A2. Pharmacol Toxicol 76:286–288.
  • Jerling, M., Lindstrom, L., Bondesson, U., Bertilsson, L. (1994). Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 16:368–374.
  • Jeurissen, S. M., Bogaards, J. J., Boersma, M. G., ter Horst, J. P., Awad, H. M., Fiamegos, Y. C., et al. (2006). Human cytochrome P450 enzymes of importance for the bioactivation of methyleugenol to the proximate carcinogen 1’-hydroxymethyleugenol. Chem Res Toxicol 19:111–116.
  • Jeurissen, S. M., Punt, A., Boersma, M. G., Bogaards, J. J., Fiamegos, Y. C., Schilter, B., et al. (2007). Human cytochrome P450 enzyme specificity for the bioactivation of estragole and related alkenylbenzenes. Chem Res Toxicol 20:798–806.
  • Jiang, Z., Dalton, T. P., Jin, L., Wang, B., Tsuneoka, Y., Shertzer, H. G., et al. (2005). Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus. Hum Mutat 25:196–206.
  • Jiang, Z., Dragin, N., Jorge-Nebert, L. F., Martin, M. V., Guengerich, F. P., Aklillu, E., et al. (2006). Search for an association between the human CYP1A2 genotype and CYP1A2 metabolic phenotype. Pharmacogenet Genomics 16:359–367.
  • Jiao, S., Liu, B., Gao, A., Ye, M., Jia, X., Zhang, F., et al. (2008). Benzo(a)pyrene-caused increased G1-S transition requires the activation of c-Jun through p53-dependent PI-3K/Akt/ERK pathway in human embryo lung fibroblasts. Toxicol Lett 178:167–175.
  • Johansson, I., Oscarson, M., Yue, Q. Y., Bertilsson, L., Sjoqvist, F., Ingelman-Sundberg, M. (1994). Genetic analysis of the Chinese cytochrome P450 2D locus: characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol 46:452–459.
  • Johnson, A. D., Zhang, Y., Papp, A. C., Pinsonneault, J. K., Lim, J. E., Saffen, D., et al. (2008). Polymorphisms affecting gene transcription and mRNA processing in pharmacogenetic candidate genes: detection through allelic expression imbalance in human target tissues. Pharmacogenet Genomics 18:781–791.
  • Jokinen, M. J., Olkkola, K. T., Ahonen, J., Neuvonen, P. J. (2003). Effect of ciprofloxacin on the pharmacokinetics of ropivacaine. Eur J Clin Pharmacol 58:653–657.
  • Jung, J., Kim, N. D., Kim, S. Y., Choi, I., Cho, K. H., Oh, W. S., et al. (2008). Regioselectivity prediction of CYP1A2-mediated Phase I metabolism. J Chem Inf Model 48:1074–1080.
  • Kadokura, T., den Adel, M., Krauwinkel, W. J., Takeshige, T., Nishida, A. (2008). The effect of fluvoxamine on the pharmacokinetics, safety, and tolerability of ramosetron in healthy subjects. Eur J Clin Pharmacol 64:691–695.
  • Kagimoto, M., Heim, M., Kagimoto, K., Zeugin, T., Meyer, U. A. (1990). Multiple mutations of the human cytochrome P450 2D6 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.
  • Kalgutkar, A. S., Nguyen, H. T., Vaz, A. D., Doan, A., Dalvie, D. K., McLeod, D. G., et al. (2003). In vitro metabolism studies on the isoxazole ring scission in the anti-inflammatory agent lefluonomide to its active α-cyanoenol metabolite A771726: mechanistic similarities with the cytochrome P450-catalyzed dehydration of aldoximes. Drug Metab Dispos 31:1240–1250.
  • Kalow, W., Tang, B. K. (1991). Caffeine as a metabolic probe: exploration of the enzyme-inducing effect of cigarette smoking. Clin Pharmacol Ther 49:44–48.
  • Kalow, W., Tang, B. K. (1993). The use of caffeine for enzyme assays: a critical appraisal. Clin Pharmacol Ther 53:503–514.
  • Kamdem, L. K., Meineke, I., Godtel-Armbrust, U., Brockmoller, J., Wojnowski, L. (2006). Dominant contribution of P450 3A4 to the hepatic carcinogenic activation of aflatoxin B1. Chem Res Toxicol 19:577–586.
  • Kaminsky, L. S., Zhang, Z. Y. (1997). Human P450 metabolism of warfarin. Pharmacol Ther 73:67–74.
  • Kanebratt, K. P., Andersson, T. B. (2008). HepaRG cells as an in vitro model for evaluation of cytochrome P450 induction in humans. Drug Metab Dispos 36:137–145.
  • Kanebratt, K. P., Diczfalusy, U., Backstrom, T., Sparve, E., Bredberg, E., Bottiger, Y., et al. (2008). Cytochrome P450 induction by rifampicin in healthy subjects: determination using the Karolinska cocktail and the endogenous CYP3A4 marker 4β-hydroxycholesterol. Clin Pharmacol Ther 84:589–594.
  • 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.
  • Karjalainen, M. J., Neuvonen, P. J., Backman, J. T. (2006). Rofecoxib is a potent, metabolism-dependent inhibitor of CYP1A2: implications for in vitro prediction of drug interactions. Drug Metab Dispos 34:2091–2096.
  • Karjalainen, M. J., Neuvonen, P. J., Backman, J. T. (2007). Tolfenamic acid is a potent CYP1A2 inhibitor in vitro but does not interact in vivo: correction for protein binding is needed for data interpretation. Eur J Clin Pharmacol 63:829–836.
  • Karjalainen, M. J., Neuvonen, P. J., Backman, J. T. (2008a). Celecoxib is a CYP1A2 inhibitor in vitro but not in vivo. Eur J Clin Pharmacol 64:511–519.
  • Karjalainen, M. J., Neuvonen, P. J., Backman, J. T. (2008b). In vitro inhibition of CYP1A2 by model inhibitors, anti-inflammatory analgesics and female sex steroids: predictability of in vivo interactions. Basic Clin Pharmacol Toxicol 103:157–165.
  • Kassahun, K., Mattiuz, E., Nyhart, E., Jr., Obermeyer, B., Gillespie, T., Murphy, A., et al. (1997). Disposition and biotransformation of the antipsychotic agent olanzapine in humans. Drug Metab Dispos 25:81–93.
  • Kaye, C. M., Nicholls, B. (2000). Clinical pharmacokinetics of ropinirole. Clin Pharmacokinet 39:243-254. Kemper, B. (2004). Structural basis for the role in protein folding of conserved proline-rich regions in cytochromes P450. Toxicol Appl Pharmacol 199:305–315.
  • Kerzee, J. K., Ramos, K. S. (2000). Activation of c-Ha-ras by benzo(a)pyrene in vascular smooth muscle cells involves redox stress and aryl hydrocarbon receptor. Mol Pharmacol 58:152–158.
  • Kick, A., Bertoli, R., Moschovitis, G., Caduff Janosa, P., Cerny, A. (2005). [Extreme sinus bradycardia (30/min) with acute right heart failure under tizanidine (Sirdalud). Possible pharmacological interaction with rofecoxib (Vioxx)]. Med Klin (Munich) 100:213–216.
  • Kim, D., Guengerich, F. P. (2004). Selection of human cytochrome P450 1A2 mutants with enhanced catalytic activity for heterocyclic amine N-hydroxylation. Biochemistry 43:981–988.
  • Kim, K. B., Seo, K. A., Yoon, Y. J., Bae, M. A., Cheon, H. G., Shin, J. G., et al. (2008). In vitro metabolism of a novel PPAR-γ agonist, KR-62980, and its stereoisomer, KR-63198, inhuman liver microsomes and by recombinant cytochrome P450s. Xenobiotica 38:1165–1176.
  • Kimura, S., Kawabe, M., Yu, A., Morishima, H., Fernandez-Salguero, P., Hammons, G. J., et al. (2003). Carcinogenesis of the food mutagen PhIP in mice is independent of CYP1A2. Carcinogenesis 24:583–587.
  • Kinzig-Schippers, M., Fuhr, U., Zaigler, M., Dammeyer, J., Rusing, G., Labedzki, A., et al. (1999). Interaction of pefloxacin and enoxacin with the human cytochrome P450 enzyme CYP1A2. Clin Pharmacol Ther 65:262–274.
  • Kirchheiner, J., Meineke, I., Muller, G., Roots, I., Brockmoller, J. (2002). Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers. Pharmacogenetics 12:571–580.
  • Kita, T., Sakaeda, T., Baba, T., Aoyama, N., Kakumoto, M., Kurimoto, Y., et al. (2003). Different contribution of CYP2C19 in the in vitro metabolism of three proton pump inhibitors. Biol Pharm Bull 26:386–390.
  • Kitamura, R., Asanoma, H., Nagayama, S., Otagiri, M. (2008). Identification of human liver cytochrome P450 isoforms involved in autoinduced metabolism of the antiangiogenic agent (Z)-5-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-propanoic acid (TSU-68). Drug Metab Dispos 36:1003–1009.
  • Kitamura, R., Yamamoto, Y., Nagayama, S., Otagiri, M. (2007). Decrease in plasma concentrations of antiangiogenic agent TSU-68 ((Z)-5-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-propanoic acid) during oral administration twice a day to rats. Drug Metab Dispos 35:1611–1616.
  • Knight, J. C. (2004). Allele-specific gene expression uncovered. Trends Genet 20:113–116.
  • Ko, J. W., Jang, I. J., Shin, J. G., Nam, S. K., Shin, S. G., Flockhart, D. A. (1999). Theophylline pharmacokinetics are not altered by lansoprazole in CYP2C19 poor metabolizers. Clin Pharmacol Ther 65:606–614.
  • Kobayashi, K., Ishizuka, T., Shimada, N., Yoshimura, Y., Kamijima, K., Chiba, K. (1999a). Sertraline N-demethylation is catalyzed by multiple isoforms of human cytochrome P450 in vitro. Drug Metab Dispos 27:763–766.
  • Kobayashi, K., Nakajima, M., Chiba, K., Yamamoto, T., Tani, M., Ishizaki, T., et al. (1998). Inhibitory effects of antiarrhythmic drugs on phenacetin O-deethylation catalysed by human CYP1A2. Br J Clin Pharmacol 45:361–368.
  • Kobayashi, K., Nakajima, M., Oshima, K., Shimada, N., Yokoi, T., Chiba, K. (1999b). Involvement of CYP2E1 as a low-affinity enzyme in phenacetin O-deethylation in human liver microsomes. Drug Metab Dispos 27:860–865.
  • Koch, K. M., Corrigan, B. W., Manzo, J., James, C. D., Scott, R. J., Stead, A. G., et al. (2004). Alosetron repeat dose pharmacokinetics, effects on enzyme activities, and influence of demographic factors. Aliment Pharmacol Ther 20:223–230.
  • Koch, K. M., Ricci, B. M., Hedayetullah, N. S., Jewell, D., Kersey, K. E. (2001). Effect of alosetron on theophylline pharmacokinetics. Br J Clin Pharmacol 52:596–600.
  • Koch, P., Hirst, D. R., von Wartburg B. R. (1989). Biological fate of sirdalud in animals and man. Xenobiotica 19:1255–1265.
  • 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, inhuman liver microsomes. Drug Metab Dispos 28:1457–1463.
  • Komoroski, B. J., Zhang, S., Cai, H., Hutzler, J. M., Frye, R., Tracy, T. S., et al. (2004). Induction and inhibition of cytochromes P450 by the St. John’s wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 32:512–518.
  • Korhonen, L. E., Rahnasto, M., Mahonen, N. J., Wittekindt, C., Poso, A., Juvonen, R. O., et al. (2005). Predictive three-dimensional quantitative structure-activity relationship of cytochrome P4501A2 inhibitors. J Med Chem 48:3808–3815.
  • Kot, M., Daniel, W. A. (2008a). The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: an in vitro comparative study with cDNA-expressed P450s including CYP2C isoforms. Biochem Pharmacol 76:543–551.
  • Kot, M., Daniel, W. A. (2008b). Relative contribution of rat cytochrome P450 isoforms to the metabolism of caffeine: the pathway and concentration dependence. Biochem Pharmacol 75:1538–1549.
  • Koutros, S., Berndt, S. I., Sinha, R., Ma, X., Chatterjee, N., Alavanja, M. C., et al. (2009). Xenobiotic metabolizing gene variants, dietary heterocyclic amine intake, and risk of prostate cancer. Cancer Res 69:1877–1884.
  • 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. (1997). 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.
  • Kozak, K. R., Abbott, B., Hankinson, O. (1997). ARNT-deficient mice and placental differentiation. Dev Biol 191:297–305.
  • Krainev, A. G., Shimizu, T., Hiroya, K., Hatano, M. (1992). Effect of mutations at Lys250, Arg251, and Lys253 of cytochrome P450 1A2 on the catalytic activities and the bindings of bifunctional axial ligands. Arch Biochem Biophys 298:198–203.
  • Krainev, A. G., Shimizu, T., Ishigooka, M., Hiroya, K., Hatano, M. (1993). Chiral recognition at cytochrome P450 1A2 active site: effects of mutations at the putative distal site on the bindings of asymmetrical axial ligands. Biochemistry 32:1951–1957.
  • Krainev, A. G., Shimizu, T., Ishigooka, M., Hiroya, K., Hatano, M., Fujii-Kuriyama, Y. (1991). Absorption spectral study of cytochrome P450d-phenyl isocyanide complexes: effects of mutations at the putative distal site on the conformational stability. Biochemistry 30:11206–11211.
  • 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.
  • 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.
  • Kroon, L. A. (2007). Drug interactions with smoking. Am J Health Syst Pharm 64:1917–1921.
  • Kubota, M., Sogawa, K., Kaizu, Y., Sawaya, T., Watanabe, J., Kawajiri, K., et al. (1991). Xenobiotic responsive element in the 5’-upstream region of the human P450C gene. J Biochem 110:232–236.
  • Kudo, S., Okumura, H., Miyamoto, G., Ishizaki, T. (1999). Cytochrome P450 isoforms involved in carboxylic acid ester cleavage of Hantzsch pyridine ester of pranidipine. Drug Metab Dispos 27:303–308.
  • Kulling, S. E., Lehmann, L., Metzler, M. (2002). Oxidative metabolism and genotoxic potential of major isoflavone phytoestrogens. J Chromatogr B Analyt Technol Biomed Life Sci 777:211–218.
  • Kunze, K. L., Trager, W. F. (1993). Isoform-selective mechanism-based inhibition of human cytochrome P450 1A2 by furafylline. Chem Res Toxicol 6:649–656.
  • Kuriya, S., Ohmori, S., Hino, M., Ishii, I., Nakamura, H., Senda, C., et al. (2000). Identification of cytochrome P-450 isoform(s) responsible for the metabolism of pimobendan in human liver microsomes. Drug Metab Dispos 28:73–78.
  • Labbe, L., Robitaille, N. M., Lefez, C., Potvin, D., Gilbert, M., O’Hara, G., et al. (2004). Effects of ciprofloxacin on the stereoselective disposition of mexiletine in man. Ther Drug Monit 26:492–498.
  • Labedzki, A., Buters, J., Jabrane, W., Fuhr, U. (2002). Differences in caffeine and paraxanthine metabolism between human and murine CYP1A2. Biochem Pharmacol 63:2159–2167.
  • Laika, B., Leucht, S., Heres, S., Schneider, H., Steimer, W. (2009). Pharmacogenetics and olanzapine treatment: CYP1A2*1F and serotonergic polymorphisms influence therapeutic outcome. Pharmacogenomics J [Epub ahead of print]
  • Lambrecht, R. W., Sinclair, P. R., Gorman, N., Sinclair, J. F. (1992). Uroporphyrinogen oxidation catalyzed by reconstituted cytochrome P450 1A2. 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.
  • Lampe, J. W., King, I. B., Li, S., Grate, M. T., Barale, K. V., Chen, C., et al. (2000). Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets. Carcinogenesis 21:1157–1162.
  • Landi, M. T., Zocchetti, C., Bernucci, I., Kadlubar, F. F., Tannenbaum, S., Skipper, P., et al. (1996). Cytochrome P4501A2: enzyme induction and genetic control in determining 4-aminobiphenyl-hemoglobin adduct levels. Cancer Epidemiol Biomarkers Prev 5:693–698.
  • Lang, D. H., Rettie, A. E. (2000). In vitro evaluation of potential in vivo probes for human flavin-containing monooxygenase (FMO): metabolism of benzydamine and caffeine by FMO and P450 isoforms. Br JClin Pharmacol 50:311–314.
  • Langouet, S., Furge, L. L., Kerriguy, N., Nakamura, K., Guillouzo, A., Guengerich, F. P. (2000). Inhibition of human cytochrome P450 enzymes by 1,2-dithiole-3-thione, oltipraz and its derivatives, and sulforaphane. Chem Res Toxicol 13:245–252.
  • 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.
  • Larsen, J. T., Hansen, L. L., Brosen, K. (1999). Tacrine is not an ideal probe drug for measuring CYP1A2 activity in vivo. Br J Clin Pharmacol 48:663–668.
  • Le Liboux, A., Cachia, J. P., Kirkesseli, S., Gautier, J. Y., Guimart, C., Montay, G., et al. (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., et al. (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.
  • Lecoq, S., Chalvet, O., Strapelias, H., Grover, P. L., Phillips, D. H., Duquesne, M. (1991). Microsomal metabolism of dibenz[a,c]anthracene, dibenz[a,h]anthracene and dibenz[a,j]anthracene to bis-dihydrodiols and polyhydroxylated products. Chem Biol Interact 80:261–279.
  • Lee, A. J., Cai, M. X., Thomas, P. E., Conney, A. H., Zhu, B. T. (2003). Characterization of the oxidative metabolites of 17β-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 17β-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, B. L., Benowitz, N. L., Jacob, P., III. (1987). Cigarette abstinence, nicotine gum, and theophylline disposition. Ann Intern Med 106:553–555.
  • Lee, H., Yeom, H., Kim, Y. G., Yoon, C. N., Jin, C., Choi, J. S., et al. (1998). Structure-related inhibition of human hepatic caffeine N3-demethylation by naturally occurring flavonoids. Biochem Pharmacol 55:1369–1375.
  • Lee, S. H., Slattery, J. T. (1997). Cytochrome P450 isozymes involved in lisofylline metabolism to pentoxifylline in human liver microsomes. Drug Metab Dispos 25:1354–1358.
  • Lee, S. W., Jang, I. J., Shin, S. G., Lee, K. H., Yim, D. S., Kim, S. W., et al. (1994). CYP1A2 activity as a risk factor for bladder cancer. J Korean Med Sci 9:482–489.
  • Lee, Y. S., Dutta, A. (2009). MicroRNAs in cancer. Annu Rev Pathol 4:199–227.
  • Lewis, D. F. (1999). Homology modelling of human cytochromes P450 involved in xenobiotic metabolism and rationalization of substrate selectivity. Exp Toxicol Pathol 51:369–374.
  • Lewis, D. F. (2000). On the recognition of mammalian microsomal cytochrome P450 substrates and their characteristics: towards the prediction of human P450 substrate specificity and metabolism. Biochem Pharmacol 60:293–306.
  • Lewis, D. F., Lake, B. G. (1996). Molecular modelling of CYP1A subfamily members based on an alignment with CYP102: rationalization of CYP1A substrate specificity in terms of active site amino acid residues. Xenobiotica 26:723–753.
  • Lewis, D. F., Lake, B. G., Dickins, M., Ueng, Y. F., Goldfarb, P. S. (2003). Homology modelling of human CYP1A2 based on the CYP2C5 crystallographic template structure. Xenobiotica 33:239–254.
  • Lewis, D. F., Lake, B. G., George, S. G., Dickins, M., Eddershaw, P. J., Tarbit, M. H., et al. (1999). Molecular modelling of CYP1 family enzymes CYP1A1, CYP1A2, CYP1A6 and CYP1B1 based on sequence homology with CYP102. Toxicology 139:53–79.
  • Lewis, D. F. V., Dickins, M. (2001). Quantitative structure-activity relationships (QSARs) within series of inhibitors for mammalian cytochromes P450 (CYPs). J Enzyme Inhibit 16:321–330.
  • Li, D., Jiao, L., Li, Y., Doll, M. A., Hein, D. W., Bondy, M. L., et al. (2006). Polymorphisms of cytochrome P450 1A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer. Carcinogenesis 27:103–111.
  • Li, J., Zhao, M., He, P., Hidalgo, M., Baker, S. D. (2007). Differential metabolism of gefitinib and erlotinib by human cytochrome P450 enzymes. Clin Cancer Res 13:3731–3737.
  • Liang, H. C., Li, H., McKinnon, R. A., Duffy, J. J., Potter, S. S., Puga, A., et al. (1996). CYP1A2 −/− null mutant mice develop normally but show deficient drug metabolism. Proc Natl Acad Sci U S A 93:1671–1676.
  • Liang, H. C., McKinnon, R. A., Nebert, D. W. (1997). Sensitivity of CYP1A1 mRNA inducibility by dioxin is the same in Cyp1a2+/+ wild-type and Cyp1a2 −/− null mutant mice. Biochem Pharmacol 54:1127–1131.
  • Lin, B. C., Sullivan, R., Lee, Y., Moran, S., Glover, E., Bradfield, C. A. (2007). Deletion of the aryl hydrocarbon receptor-associated protein 9 leads to cardiac malformation and embryonic lethality. J Biol Chem 282:35924–35932.
  • 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, L. Y., Di Stefano, E. W., Schmitz, D. A., Hsu, L., Ellis, S. W., Lennard, M. S., et al. (1997). Oxidation of methamphetamine and methylenedioxymethamphetamine by CYP2D6. Drug Metab Dispos 25:1059–1064.
  • Linnet, K. (2002). Glucuronidation of olanzapine by cDNA-expressed human UDP-glucuronosyltransferases and human liver microsomes. Hum Psychopharmacol 17:233–238.
  • Liu, H. X., Hu, Y., Liu, Y., He, Y. Q., Li, W., Yang, L. (2009). CYP1A2 is the major isoform responsible for paeonol O-demethylation in human liver microsomes. Xenobiotica 23:672–679.
  • Liu, J., Ericksen, S. S., Sivaneri, M., Besspiata, D., Fisher, C. W., Szklarz, G. D. (2004). The effect of reciprocal active site mutations in human cytochromes P450 1A1 and 1A2 on alkoxyresorufin metabolism. Arch Biochem Biophys 424:33–43.
  • Liu, N., Zhang, Q. Y., Vakharia, D., Dunbar, D., Kaminsky, L. S. (2001). Induction of CYP1A by benzo[k]fluoranthene in human hepatocytes: CYP1A1 or CYP1A2? Arch Biochem Biophys 389:130–134.
  • Lobo, E. D., Bergstrom, R. F., Reddy, S., Quinlan, T., Chappell, J., Hong, Q., et al. (2008). In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clin Pharmacokinet 47:191–202.
  • Logroscino, G., Armon, C. (2007). Amyotrophic lateral sclerosis: a global threat with a possible difference in risk across ethnicities. Neurology 68:E17.
  • Long, L., Dolan, M. E. (2001). Role of cytochrome P450 isoenzymes in metabolism of O6-benzylguanine: implications for dacarbazine activation. Clin Cancer Res 7:4239–4244.
  • Lozano, J. J., Lopez-de-Brinas, E., Centeno, N. B., Guigo, R., Sanz, F. (1997). Three-dimensional modelling of human cytochrome P450 1A2 and its interaction with caffeine and MeIQ. J Comput Aided Mol Des 11:395–408.
  • Lozano, J. J., Pastor, M., Cruciani, G., Gaedt, K., Centeno, N. B., Gago, F., et al. (2000). 3D-QSAR methods on the basis of ligand-receptor complexes. Application of COMBINE and GRID/GOLPE methodologies to a series of CYP1A2 ligands. J Comput Aided Mol Des 14:341–353.
  • Lu, M. L., Lane, H. Y., Chen, K. P., Jann, M. W., Su, M. H., Chang, W. H. (2000). Fluvoxamine reduces the clozapine dosage needed in refractory schizophrenic patients. J Clin Psychiatry 61:594–599.
  • Lu, P., Schrag, M. L., Slaughter, D. E., Raab, C. E., Shou, M., Rodrigues, A. D. (2003). Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. Drug Metab Dispos 31:1352–1360.
  • 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.
  • Ma, B., Prueksaritanont, T., Lin, J. H. (2000). Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos 28:125–130.
  • Ma, Q. (2001). Induction of CYP1A1. The AhR/DRE paradigm: transcription, receptor regulation, and expanding biological roles. Curr Drug Metab 2:149–164.
  • Ma, Q., Lu, A. Y. (2007). CYP1A induction and human risk assessment: an evolving tale of in vitro and in vivo studies. Drug Metab Dispos 35:1009–1016.
  • 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.
  • Madan, A., Fisher, A., Jin, L., Chapman, D., Bozigian, H. P. (2007). In vitro metabolism of indiplon and an assessment of its drug interaction potential. Xenobiotica 37:736–752.
  • Madan, A., Graham, R. A., Carroll, K. M., Mudra, D. R., Burton, L. A., Krueger, L. A., et al. (2003). Effects of prototypical microsomal enzyme inducers on cytochrome P450 expression in cultured human hepatocytes. Drug Metab Dispos 31:421–431.
  • Madden, S., Woolf, T. F., Pool, W. F., Park, B. K. (1993). An investigation into the formation of stable, protein-reactive and cytotoxic metabolites from tacrine in vitro. Studies with human and rat liver microsomes. Biochem Pharmacol 46:13–20.
  • Maes, M., Westenberg, H., Vandoolaeghe, E., Demedts, P., Wauters, A., Neels, H., et al. (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.
  • Magnusson, M. O., Dahl, M. L., Cederberg, J., Karlsson, M. O., Sandstrom, R. (2008). Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and P-gp as assessed by probe substrates midazolam, caffeine, and digoxin. Clin Pharmacol Ther 84:52–62.
  • Malanga, G., Reiter, R. D., Garay, E. (2008). Update on tizanidine for muscle spasticity and emerging indications. Expert Opin Pharmacother 9:2209–2215.
  • Malfatti, M. A., Ubick, E. A., Felton, J. S. (2005). The impact of glucuronidation on the bioactivation and DNA adduction of the cooked-food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in vivo. Carcinogenesis 26:2019–2028.
  • 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.
  • Marshall, M. E., Mohler, J. L., Edmonds, K., Williams, B., Butler, K., Ryles, M., et al. (1994). An updated review of the clinical development of coumarin (1,2-benzopyrone) and 7-hydroxycoumarin. J Cancer Res Clin Oncol 120(Suppl):S39-S42.
  • Martinez, C., Albet, C., Agundez, J. A., Herrero, E., Carrillo, J. A., Marquez, M., et al. (1999). Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther 65:369–376.
  • Masubuchi, Y., Horie, T. (1998). Dihydralazine-induced inactivation of cytochrome P450 enzymes in rat liver microsomes. Drug Metab Dispos 26:338–342.
  • Masubuchi, Y., Horie, T. (1999). Mechanism-based inactivation of cytochrome P450s 1A2 and 3A4 by dihydralazine in human liver microsomes. ChemRes Toxicol 12:1028–1032.
  • Masubuchi, Y., Hosokawa, S., Horie, T., Suzuki, T., Ohmori, S., Kitada, M., et al. (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., Nakano, T., Ose, A., Horie, T. (2001). Differential selectivity in carbamazepine-induced inactivation of cytochrome P450 enzymes in rat and human liver. Arch Toxicol 75:538–543.
  • Maurel, P. (1996). The use of adult human hepatocytes in primary culture and other in vitro systems to investigate drug metabolism in man. Adv Drug Deliv Rev 22:105–132.
  • Mayo, P. R. (2001). Effect of passive smoking on theophylline clearance in children. Ther Drug Monit 23:503–505.
  • Mayuzumi, H., Sambongi, C., Hiroya, K., Shimizu, T., Tateishi, T., Hatano, M. (1993). Effect of mutations of ionic amino acids of cytochrome P450 1A2 on catalytic activities toward 7-ethoxycoumarin and methanol. Biochemistry 32:5622–5628.
  • Mayuzumi, H., Shimizu, T., Sambongi, C., Hiroya, K., Hatano, M. (1994). Essential role of His163 of cytochrome P450 1A2 in catalytic functions associated with cytochrome b5. Arch Biochem Biophys 310:367–372.
  • McEnroe, J. D., Fleishaker, J. C. (2005). Clinical pharmacokinetics of almotriptan, a serotonin 5-HT1B/1D receptor agonist for the treatment of migraine. Clin Pharmacokinet 44:237–246.
  • Mega, J. L., Close, S. L., Wiviott, S. D., Shen, L., Hockett, R. D., Brandt, J. T., et al. (2009). Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 119:2553–2560.
  • Melendez-Colon, V. J., Luch, A., Seidel, A., Baird, W. M. (1999). Cancer initiation by polycyclic aromatic hydrocarbons results from formation of stable DNA adducts rather than apurinic sites. Carcinogenesis 20:1885–1891.
  • 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., 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., et al. (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.
  • Meunier, V., Bourrie, M., Julian, B., Marti, E., Guillou, F., Berger, Y., et al. (2000). Expression and induction of CYP1A1/1A2, CYP2A6 and CYP3A4 in primary cultures of human hepatocytes: a 10-year follow-up. Xenobiotica 30:589–607.
  • Meyer, M. R., Peters, F. T., Maurer, H. H. (2009). Stereoselective differences in the cytochrome P450-dependent dealkylation and demethylenation of N-methyl-benzodioxolyl-butanamine (MBDB, Eden) enantiomers. Biochem Pharmacol 77:1725–1734.
  • Mihara, K., Kondo, T., Suzuki, A., Yasui-Furukori, N., Ono, S., Otani, K., et al. (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.
  • 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.
  • Miller, M., Opheim, K. E., Raisys, V. A., Motulsky, A. G. (1984). Theophylline metabolism: variation and genetics. Clin Pharmacol Ther 35:170–182.
  • 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.
  • Mise, M., Hashizume, T., Komuro, S. (2008). Characterization of substrate specificity of dog CYP1A2 using CYP1A2-deficient and wild-type dog liver microsomes. Drug Metab Dispos 36:1903–1908.
  • Mishra, H. N., Das, C. (2003). A review on biological control and metabolism of aflatoxin. Crit Rev Food Sci Nutr 43:245–264.
  • Momo, K., Doki, K., Hosono, H., Homma, M., Kohda, Y. (2004). Drug interaction of tizanidine and fluvoxamine. Clin Pharmacol Ther 76:509–510.
  • Morrison, H. G., Oleksiak, M. F., Cornell, N. W., Sogin, M. L., Stegeman, J. J. (1995). Identification of cytochrome P450 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.
  • Murayama, N., Soyama, A., Saito, Y., Nakajima, Y., Komamura, K., Ueno, K., et al. (2004). Six novel nonsynonymous CYP1A2 gene polymorphisms: catalytic activities of the naturally occurring variant enzymes. J Pharmacol Exp Ther 308:300–306.
  • Murray, I. A., Perdew, G. H. (2008). Omeprazole stimulates the induction of human insulin-like growth factor binding protein-1 through aryl hydrocarbon receptor activation. J Pharmacol Exp Ther 324:1102–1110.
  • Musani, S. K., Shriner, D., Liu, N., Feng, R., Coffey, C. S., Yi, N., et al. (2007). Detection of gene × gene interactions in genome-wide association studies of human population data. Hum Hered 63:67–84.
  • Muscat, J. E., Pittman, B., Kleinman, W., Lazarus, P., Stellman, S. D., Richie, J. P., Jr. (2008). Comparison of CYP1A2 and NAT2 phenotypes between black and white smokers. Biochem Pharmacol 76:929–937.
  • Muschler, E., Lal, J., Jetter, A., Rattay, A., Zanger, U., Zadoyan, G., et al. (2009). The role of human CYP2C8 and CYP2C9 variants in pioglitazone metabolism in vitro. Basic Clin Pharmacol Toxicol [Epub ahead of print].
  • Mutlib, A. E., Klein, J. T. (1998). Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther 286:1285–1293.
  • Myrand, S. P., Sekiguchi, K., Man, M. Z., Lin, X., Tzeng, R. Y., Teng, C. H., et al. (2008). Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations. Clin Pharmacol Ther 84:347–361.
  • Nakajima, M., Iwanari, M., Yokoi, T. (2003). Effects of histone deacetylation and DNA methylation on the constitutive and TCDD-inducible expressions of the human CYP1 family in MCF-7 and HeLa cells. Toxicol Lett 144:247–256.
  • 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., Nakamura, S., Tokudome, S., Shimada, N., Yamazaki, H., Yokoi, T. (1999a). Azelastine N-demethylation by CYP3A4, 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., 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.
  • Nakamura, K., Ariyoshi, N., Yokoi, T., Ohgiya, S., Chida, M., Nagashima, K., et al. (2002). CYP2D6.10 present in human liver microsomes shows low catalytic activity and thermal stability. Biochem Biophys Res Commun 293:969–973.
  • Nakano, R., Sato, H., Watanabe, A., Ito, O., Shimizu, T. (1996). Conserved Glu318 at the cytochrome P450 1A2 distal site is crucial in the nitric oxide complex stability. J Biol Chem 271:8570–8574.
  • Narimatsu, S., Yonemoto, R., Masuda, K., Katsu, T., Asanuma, M., Kamata, T., et al. (2008). Oxidation of 5-methoxy-N,N-diisopropyltryptamine in rat liver microsomes and recombinant cytochrome P450 enzymes. Biochem Pharmacol 75:752–760.
  • Narimatsu, S., Yonemoto, R., Saito, K., Takaya, K., Kumamoto, T., Ishikawa, T., et al. (2006). Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes. Biochem Pharmacol 71:1377–1385.
  • Nassar, A. F., King, I., Paris, B. L., Haupt, L., Ndikum-Moffor, F., Campbell, R., et al. (2009). An in vitro evaluation of the victim and perpetrator potential of the anti-cancer agent laromustine (VNP40101M), based on reaction phenotyping and inhibition and induction of cytochrome P450 (CYP) enzymes. Drug Metab Dispos 37:1922–1930.
  • Nebert, D. W., Dalton, T. P., Okey, A. B., Gonzalez, F. J. (2004). Role of aryl hydrocarbon receptor-mediated induction of the CYP1 enzymes in environmental toxicity and cancer. J Biol Chem 279:23847–23850.
  • 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.
  • 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.
  • Noguchi, K., Mera, A., Watanabe, T., Higuchi, S., Chiba, K. (2000). Identification of cytochrome P450 isoform involved in the metabolism of YM992, a novel selective serotonin re-uptake inhibitor, in human liver microsomes. Xenobiotica 30:503–513.
  • 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.
  • Obase, Y., Shimoda, T., Kawano, T., Saeki, S., Tomari, S. Y., Mitsuta-Izaki, K., et al. (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. (2001). 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., et al. (1995). Metabolism of a new local anesthetic, ropivacaine, by human hepatic cytochrome P450. Anesthesiology 82:214–220.
  • Oda, Y., Hirayama, T., Watanabe, T. (2009). Genotoxic activation of the environmental pollutant 3,6-dinitrobenzo[e]pyrene in Salmonella typhimuriumumu strains expressing human cytochrome P450 and N-acetyltransferase. Toxicol Lett 188:258–262.
  • Oganesian, A., Shilling, A. D., Young-Sciame, R., Tran, J., Watanyar, A., Azam, F., et al. (2009). Desvenlafaxine and venlafaxine exert minimal in vitro inhibition of human cytochrome P450 and P-glycoprotein activities. Psychopharmacol Bull 42:47–63.
  • Ogiso, H., Kagi, N., Matsumoto, E., Nishimoto, M., Arai, R., Shirouzu, M., et al. (2004). Phosphorylation analysis of 90 kDa heat shock protein within the cytosolic arylhydrocarbon receptor complex. Biochemistry 43:15510–15519.
  • Ohmori, S., Takeda, S., Rikihisa, T., Kiuchi, M., Kanakubo, Y., Kitada, M. (1993). Studies on cytochrome P450 responsible for oxidative metabolism of imipramine in human liver microsomes. Biol Pharm Bull 16:571–575.
  • Ohyama, K., Nakajima, M., Suzuki, M., Shimada, N., Yamazaki, H., Yokoi, T. (2000). Inhibitory effects of amiodarone and its N-deethylated metabolite on human cytochrome P450 activities: prediction of in vivo drug interactions. Br J Clin Pharmacol 49:244–253.
  • Okey, A. B., Vella, L. M., Harper, P. A. (1989). Detection and characterization of a low affinity form of cytosolic Ah receptor in livers of mice nonresponsive to induction of cytochrome P450 1 by 3-methylcholanthrene. Mol Pharmacol 35:823–830.
  • Olesen, O. V., Linnet, K. (1997). Hydroxylation and demethylation of the tricyclic antidepressant nortriptyline by cDNA-expressed human cytochrome P450 isozymes. Drug Metab Dispos 25:740–744.
  • 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.
  • 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., et al. (2007). NAT2 and CYP1A2 polymorphisms and lung cancer risk in relation to smoking status. Asian Pac J Cancer Prev 8:103–108.
  • Otake, Y., Walle, T. (2002). Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9. Drug Metab Dispos 30:103–105.
  • Ou-Yang, D. S., Huang, S. L., Wang, W., Xie, H. G., Xu, Z. H., Shu, Y., et al. (2000). Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population. Br J Clin Pharmacol 49:145–151.
  • Ozdemir, V., Kalow, W., Okey, A. B., Lam, M. S., Albers, L. J., Reist, C., et al. (2001a). 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., Kalow, W., Posner, P., Collins, E. J., Kennedy, J. L., Tang, B. K., et al. (2001b). CYP1A2 activity as measured by a caffeine test predicts clozapine and active metabolite steady-state concentrationin patients with schizophrenia. J Clin Psychopharmacol 21:398–407.
  • Palatini, P., Ceolotto, G., Ragazzo, F., Dorigatti, F., Saladini, F., Papparella, I., et al. (2009). CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertens 27:1594–1601.
  • Pan, M. H., Ho, C. T. (2008). Chemopreventive effects of natural dietary compounds on cancer development. Chem Soc Rev 37:2558–2574.
  • Pan, W. J., Goldwater, D. R., Zhang, Y., Pilmer, B. L., Hunt, R. H. (2000). Lack of a pharmacokinetic interaction between lansoprazole or pantoprazole and theophylline. Aliment Pharmacol Ther 14:345–352.
  • Pan, Y. Z., Gao, W., Yu, A. M. (2009). MicroRNAs regulate CYP3A4 expression via direct and indirect targeting. Drug Metab Dispos 37:2112–2117.
  • Parikh, A., Josephy, P. D., Guengerich, F. P. (1999). Selection and characterization of human cytochrome P450 1A2 mutants with altered catalytic properties. Biochemistry 38:5283–5289.
  • Paris, B. L., Ogilvie, B. W., Scheinkoenig, J. A., Ndikum-Moffor, F., Gibson, R., Parkinson, A. (2009). In vitro inhibition and induction of human liver cytochrome P450 (CYP) enzymes by milnacipran. Drug Metab Dispos 28:664–671.
  • Parker, A. C., Pritchard, P., Preston, T., Choonara, I. (1998). Induction of CYP1A2 activity by carbamazepine in children using the caffeine breath test. Br J Clin Pharmacol 45:176–178.
  • Parkinson, A., Hurwitz, A. (1991). Omeprazole and the induction of human cytochrome P450: a response to concerns about potential adverse effects. Gastroenterology 100:1157–1164.
  • Pastinen, T., Sladek, R., Gurd, S., Sammak, A., Ge, B., Lepage, P., et al. (2004). A survey of genetic and epigenetic variation affecting human gene expression. Physiol Genomics 16:184–193.
  • Pastrakuljic, A., Tang, B. K., Roberts, E. A., Kalow, W. (1997). Distinction of CYP1A1 and CYP1A2 activity by selective inhibition using fluvoxamine and isosafrole. Biochem Pharmacol 53:531–538.
  • Pavanello, S., B’Chir, F., Pulliero, A., Saguem, S., Ben Fraj, R. El, Aziz Hayouni, A. et, al. (2007). Interaction between CYP1A2-T2467DELT polymorphism and smoking in adenocarcinoma and squamous cell carcinoma of the lung. Lung Cancer 57:266–272.
  • Pavanello, S., Pulliero, A., Lupi, S., Gregorio, P., Clonfero, E. (2005). Influence of the genetic polymorphism in the 5’-noncoding region of the CYP1A2 gene on CYP1A2 phenotype and urinary mutagenicity in smokers. Mutat Res 587:59–66.
  • Pavanello, S., Simioli, P., Lupi, S., Gregorio, P., Clonfero, E. (2002). Exposure levels and cytochrome P450 1A2 activity, but not N-acetyltransferase, glutathione S-transferase (GST) M1 and T1, influence urinary mutagen excretion in smokers. Cancer Epidemiol Biomarkers Prev 11:998–1003.
  • Paxton, J. W., Kestell, P., Chiang, D., Zhou, S., Lewis, D. F. (2005). Inhibition of human CYP1A2 oxidation of 5,6-dimethyl-xanthenone-4-acetic acid by acridines: a molecular modelling study. Clin Exp Pharmacol Physiol 32:633–639.
  • Pearce, R. E., Gotschall, R. R., Kearns, G. L., Leeder, J. S. (2001). Cytochrome P450 involvement in the biotransformation of cisapride and racemic norcisapride in vitro: differential activity of individual human CYP3A isoforms. Drug Metab Dispos 29:1548–1554.
  • Pearce, R. E., Vakkalagadda, G. R., Leeder, J. S. (2002). Pathways of carbamazepine bioactivation in vitro I. Characterization of human cytochromes P450 responsible for the formation of 2- and 3-hydroxylated metabolites. Drug Metab Dispos 30:1170–1179.
  • Pelkonen, O., Myllynen, P., Taavitsainen, P., Boobis, A. R., Watts, P., Lake, B. G., et al. (2001). Carbamazepine: a ‘blind’ assessment of CYP-associated metabolism and interactions in human liver-derived in vitro systems. Xenobiotica 31:321–343.
  • Penzak, S. R., Hon, Y. Y., Lawhorn, W. D., Shirley, K. L., Spratlin, V., Jann, M. W. (2002). Influence of ritonavir on olanzapine pharmacokinetics in healthy volunteers. J Clin Psychopharmacol 22:366–370.
  • Persson, K. P., Ekehed, S., Otter, C., Lutz, E. S., McPheat, J., Masimirembwa, C. M., et al. (2006). Evaluation of human liver slices and reporter gene assays as systems for predicting the cytochrome P450 induction potential of drugs in vivo in humans. Pharm Res 23:56–69.
  • Perucca, E., Gatti, G., Spina, E. (1994). Clinical pharmacokinetics of fluvoxamine. Clin Pharmacokinet 27:175–190.
  • Peters, F. T., Meyer, M. R., Theobald, D. S., Maurer, H. H. (2008). Identification of cytochrome P450 enzymes involved in the metabolism of the new designer drug 4’-methyl-α-pyrrolidinobutyrophenone. Drug Metab Dispos 36:163–168.
  • Petersen, M. S., Halling, J., Damkier, P., Nielsen, F., Grandjean, P., Weihe, P., et al. (2006). Caffeine N3-demethylation (CYP1A2) in a population with an increased exposure to polychlorinated biphenyls. Eur J Clin Pharmacol 62:1041–1048.
  • Peterson, T. C., Peterson, M. R., Wornell, P. A., Blanchard, M. G., Gonzalez, F. J. (2004). Role of CYP1A2 and CYP2E1 in the pentoxifylline ciprofloxacin drug interaction. Biochem Pharmacol 68:395–402.
  • Petrulis, J. R., Hord, N. G., Perdew, G. H. (2000). Subcellular localization of the aryl hydrocarbon receptor is modulated by the immunophilin homolog hepatitis B virus X-associated protein 2. J Biol Chem 275:37448–37453.
  • Petrulis, J. R., Kusnadi, A., Ramadoss, P., Hollingshead, B., Perdew, G. H. (2003). The hsp90 co-chaperone XAP2 alters importin-β recognition of the bipartite nuclear localization signal of the Ah receptor and represses transcriptional activity. J Biol Chem 278:2677–2685.
  • Phillips, D. H., Hanawalt, P. C., Miller, J. A., Miller, E. C. (1981). The in vivo formation and repair of DNA adducts from 1’-hydroxysafrole. J Supramol Struct Cell Biochem 16:83–90.
  • Phillips, P. C. (2008). Epistasis — the essential role of gene interactions in the structure and evolution of genetic systems. Nat Rev Genet 9:855–867.
  • Pichard, L., Gillet, G., Bonfils, C., Domergue, J., Thenot, J. P., Maurel, P. (1995). Oxidative metabolism of zolpidem by human liver cytochrome P450s. Drug Metab Dispos 23:1253–1262.
  • Piver, B., Berthou, F., Dreano, Y., Lucas, D. (2003). Differential inhibition of human cytochrome P450 enzymes by ϵ-viniferin, the dimer of resveratrol: comparison with resveratrol and polyphenols from alcoholized beverages. Life Sci 73:1199–1213.
  • Piver, B., Fer, M., Vitrac, X., Merillon, J. M., Dreano, Y., Berthou, F., et al. (2004). Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes. Biochem Pharmacol 68:773–782.
  • Polasek, T. M., Elliot, D. J., Somogyi, A. A., Gillam, E. M., Lewis, B. C., Miners, J. O. (2006). An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid. Br J Clin Pharmacol 61:570–584.
  • Porubsky, P. R., Meneely, K. M., Scott, E. E. (2008). Structures of human cytochrome P450 2E1. Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates. J Biol Chem 283:33698–33707.
  • Poulos, T. L., Finzel, B. C., Gunsalus, I. C., Wagner, G. C., Kraut, J. (1985). The 2.6-Å crystal structure of Pseudomonas putida cytochrome P450. J Biol Chem 260:16122–16130.
  • Poulos, T. L., Finzel, B. C., Howard, A. J. (1987). High-resolution crystal structure of cytochrome P450cam. J Mol Biol 195:687–700.
  • Pucci, L., Geppetti, A., Maggini, V., Lucchesi, D., Maria Rossi, A., Longo, V. (2007). CYP1A2 F21L and F186L polymorphisms in an Italian population sample. Drug Metab Pharmacokinet 22:220–222.
  • Qiu, F., Zhang, R., Sun, J., Jiye, A., Hao, H., Peng, Y., et al. (2008). Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Drug Metab Dispos 36:1308–1314.
  • Quattrochi, L. C., Tukey, R. H. (1989). The human cytochrome CYP1A2 gene contains regulatory elements responsive to 3-methylcholanthrene. Mol Pharmacol 36:66–71.
  • Raaska, K., Neuvonen, P. J. (2000). Ciprofloxacin increases serum clozapine and N-desmethylclozapine: a study in patients with schizophrenia. Eur J Clin Pharmacol 56:585–589.
  • Racha, J. K., Rettie, A. E., Kunze, K. L. (1998). Mechanism-based inactivation of human cytochrome P450 1A2 by furafylline: detection of a 1:1 adduct to protein and evidence for the formation of a novel imidazomethide intermediate. Biochemistry 37:7407–7419.
  • Rakhit, A., Pantze, M. P., Fettner, S., Jones, H. M., Charoin, J. E., Riek, M., et al. (2008). The effects of CYP3A4 inhibition on erlotinib pharmacokinetics: computer-based simulation (SimCYP) predicts in vivo metabolic inhibition. Eur J Clin Pharmacol 64:31–41.
  • 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.
  • Rasmussen, B. B., Maenpaa, J., Pelkonen, O., Loft, S., Poulsen, H. E., Lykkesfeldt, J., et al. (1995). Selective serotonin reuptake inhibitors and theophylline metabolism inhuman liver microsomes: potent inhibition by fluvoxamine. Br JClin Pharmacol 39:151–159.
  • Rawden, H. C., Kokwaro, G. O., Ward, S. A., Edwards, G. (2000). Relative contribution of cytochromes P450 and flavin-containing monoxygenases to the metabolism of albendazole by human liver microsomes. Br J Clin Pharmacol 49:313–322.
  • 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.
  • Renwick, A. B., Watts, P. S., Edwards, R. J., Barton, P. T., Guyonnet, I., Price, R. J., et al. (2000). Differential maintenance of cytochrome P450 enzymes in cultured precision-cut human liver slices. Drug Metab Dispos 28:1202–1209.
  • Reuber, M. D. (1980). Carcinogenicity and toxicity of methoxychlor. Environ Health Perspect 36:205–219.
  • Richelson, E., Nelson, A. (1984). Antagonism by neuroleptics of neurotransmitter receptors of normal human brain in vitro. Eur J Pharmacol 103:197–204.
  • Ring, B. J., Catlow, J., Lindsay, T. J., Gillespie, T., Roskos, L. K., Cerimele, B. J., et al. (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.
  • Rizzo, N., Padoin, C., Palombo, S., Scherrmann, J. M., Girre, C. (1996). Omeprazole and lansoprazole are not inducers of cytochrome P4501A2 under conventional therapeutic conditions. Eur J Clin Pharmacol 49:491–495.
  • Roberts, R. C., Part, N. J., Pokorny, R., Muir, C., Leslie, G. C., Emre, M. (1994). Pharmacokinetics and pharmacodynamics of tizanidine. Neurology 44:S29–31.
  • Rosatelli, M. C., Meloni, A., Faa, V., Saba, L., Crisponi, G., Clemente, M. G., et al. (1997). Molecular analysis of patients of Sardinian descent with Crigler-Najjar syndrome Type I. J Med Genet 34:122–125.
  • Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., et al. (1993). Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62.
  • Rost, K. L., Brosicke, H., Brockmoller, J., Scheffler, M., Helge, H., Roots, I. (1992). Increase of cytochrome P450 1A2 activity by omeprazole: evidence by the 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. Clin Pharmacol Ther 52:170–180.
  • Rost, K. L., Fuhr, U., Thomsen, T., Zaigler, M., Brockmoller, J., Bohnemeier, H., et al. (1999). Omeprazole weakly inhibits CYP1A2 activity in man. Int J Clin Pharmacol Ther 37:567–574.
  • Rost, K. L., Roots, I. (1994). Accelerated caffeine metabolism after omeprazole treatment is indicated by urinary metabolite ratios: coincidence with plasma clearance and breath test. Clin Pharmacol Ther 55:402–411.
  • Rostami-Hodjegan, A., Amin, A. M., Spencer, E. P., Lennard, M. S., Tucker, G. T., Flanagan, R. J. (2004). Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol 24:70–78.
  • Rostami-Hodjegan, A., Nurminen, S., Jackson, P. R., Tucker, G. T. (1996). Caffeine urinary metabolite ratios as markers of enzyme activity: a theoretical assessment. Pharmacogenetics 6:121–149.
  • 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., et al. (2006). Crystal structure of human cytochrome P450 2D6. J Biol Chem 281:7614–7622.
  • Roy, K., Roy, P. P. (2008). Comparative QSAR studies of CYP1A2 inhibitor flavonoids using 2D and 3D descriptors. Chem Biol Drug Des 72:370–382.
  • Roy, S. K., Korzekwa, K. R., Gonzalez, F. J., Moschel, R. C., Dolan, M. E. (1995). Human liver oxidative metabolism of O6-benzylguanine. Biochem Pharmacol 50:1385–1389.
  • Roymans, D., Annaert, P., Van Houdt J., Weygers, A., Noukens, J., Sensenhauser, C., et al. (2005). Expression and induction potential of cytochromes P450 in human cryopreserved hepatocytes. Drug Metab Dispos 33:1004–1016.
  • Rozman, B. (2002). Clinical pharmacokinetics of leflunomide. Clin Pharmacokinet 41:421–430.
  • Ryu, J. Y., Song, I. S., Sunwoo, Y. E., Shon, J. H., Liu, K. H., Cha, I. J., et al. (2007). Development of the “Inje cocktail” for high-throughput evaluation of five human cytochrome P450 isoforms in vivo. Clin Pharmacol Ther 82:531–540.
  • Sachse, C., Bhambra, U., Smith, G., Lightfoot, T. J., Barrett, J. H., Scollay, J., et al. (2003). Polymorphisms in the cytochrome P450 CYP1A2 gene (CYP1A2) in colorectal cancer patients and controls: allele frequencies, linkage disequilibrium and influence on caffeine metabolism. Br J Clin Pharmacol 55:68–76.
  • 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.
  • Sahi, J., Hamilton, G., Sinz, M., Barros, S., Huang, S. M., Lesko, L. J., et al. (2000). Effect of troglitazone on cytochrome P450 enzymes in primary cultures of human and rat hepatocytes. Xenobiotica 30:273–284.
  • Saito, Y., Hanioka, N., Maekawa, K., Isobe, T., Tsuneto, Y., Nakamura, R., et al. (2005). Functional analysis of three CYP1A2 variants found in a Japanese population. Drug Metab Dispos 33:1905–1910.
  • Salonen, J. S., Nyman, L., Boobis, A. R., Edwards, R. J., Watts, P., Lake, B. G., et al. (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.
  • 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.
  • Sangrajrang, S., Sato, Y., Sakamoto, H., Ohnami, S., Laird, N. M., Khuhaprema, T., et al. (2009). Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women. Int J Cancer 125:837–843.
  • Sangster, S. A., Caldwell, J., Hutt, A. J., Anthony, A., Smith, R. L. (1987). The metabolic disposition of [methoxy-14C]-labelledtrans-anethole, estragole and p-propylanisole in human volunteers. Xenobiotica 17:1223–1232.
  • Sansen, S., Yano, J. K., Reynald, R. L., Schoch, G. A., Griffin, K. J., Stout, C. D., et al. (2007). Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J Biol Chem 282:14348–14355.
  • Sanz, F., Lopez-de-Brinas, E., Rodriques, J., Manaut, F. (1994). Theoretical study on the metabolism of caffeine by cytochrome P-450 1A2 and its inhibition. Quant Struct-Act Relat 13:281–284.
  • Sarich, T., Kalhorn, T., Magee, S., al-Sayegh, F., Adams, S., Slattery, J., et al. (1997). The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin. Clin Pharmacol Ther 62:21–28.
  • Sarkar, M. A., Hunt, C., Guzelian, P. S., Karnes, H. T. (1992). Characterization of human liver cytochromes P450 involved in theophylline metabolism. Drug Metab Dispos 20:31–37.
  • Sarkar, M. A., Jackson, B. J. (1994). Theophylline N-demethylations as probes for P450 1A1 and P450 1A2. Drug Metab Dispos 22:827–834.
  • Savas, U., Carstens, C. P., Jefcoate, C. R. (1997). Biological oxidations and P450 reactions. Recombinant mouse CYP1B1 expressed in Escherichia coli exhibits selective binding by polycyclic hydrocarbons and metabolism which parallels C3H10T1/2 cell microsomes, but differs from human recombinant CYP1B1. Arch Biochem Biophys 347:181–192.
  • Sawynok, J. (1995). Pharmacological rationale for the clinical use of caffeine. Drugs 49:37–50.
  • Schmeiser, H. H., Frei, E., Wiessler, M., Stiborova, M. (1997). Comparison of DNA adduct formation by aristolochic acids in various in vitro activation systems by 32P-post-labelling: evidence for reductive activation by peroxidases. Carcinogenesis 18:1055–1062.
  • 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.
  • Schulz, H. U., Hartmann, M., Steinijans, V. W., Huber, R., Luhrmann, B., Bliesath, H., et al. (1996). Lack of influence of pantoprazole on the disposition kinetics of theophylline in man. Int J Clin Pharmacol Ther 34:S51-S57.
  • Schwartz, J. I., Bugianesi, K. J., Ebel, D. L., De Smet, M., Haesen, R., Larson, P. J., et al. (2000). The effect of rofecoxib on the pharmacodynamics and pharmcokinetics of warfarin. Clin Pharmacol Ther 68:626–636.
  • Scott, E. E., White, M. A., He, Y. A., Johnson, E. F., Stout, C. D., Halpert, J. R. (2004). Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-Å resolution: insight into the range of P450 conformations and the coordination of redox partner binding. J Biol Chem 279:27294–27301.
  • Segura, J., Garcia, I., Tarrus, E. (1986). Some pharmacokinetic characteristics of furafylline, a new 1,3,8-trisubstituted xanthine. J Pharm Pharmacol 38:615–618.
  • Seppala, N. H., Leinonen, E. V., Lehtonen, M. L., Kivisto, K. T. (1999). Clozapine serum concentrations are lower in smoking than in nonsmoking schizophrenic patients. Pharmacol Toxicol 85:244–246.
  • Shahidi, N. T. (1967). Acetophenetidin sensitivity. Am J Dis Child 113:81–82.
  • 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.
  • Shimada, T., Gillam, E. M., Oda, Y., Tsumura, F., Sutter, T. R., Guengerich, F. P., et al. (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., et al. (1996). Activation of chemically diverse procarcinogens by human cytochrome P450 1B1. Cancer Res 56:2979–2984.
  • Shimada, T., Murayama, N., Okada, K., Funae, Y., Yamazaki, H., Guengerich, F. P. (2007). Different mechanisms for inhibition of human cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic inhibitors. Chem Res Toxicol 20:489–496.
  • Shimada, T., Yamazaki, H., Foroozesh, M., Hopkins, N. E., Alworth, W. L., Guengerich, F. P. (1998). Selectivity of polycyclic inhibitors for human cytochrome P450s 1A1, 1A2, and 1B1. Chem Res Toxicol 11:1048–1056.
  • Shimizu, T., Hirano, K., Takahashi, M., Hatano, M., Fujii-Kuriyama, Y. (1988). Site-directed mutageneses of rat liver cytochrome P-450d: axial ligand and heme incorporation. Biochemistry 27:4138–4141.
  • Shimizu, T., Ito, O., Hatano, M., Fujii-Kuriyama, Y. (1991a). CO binding studies of engineered cytochrome P450ds: effects of mutations at putative distal sites in the presence of polycyclic hydrocarbons. Biochemistry 30:4659–4662.
  • Shimizu, T., Murakami, Y., Hatano, M. (1994). Glu318 and Thr319 mutations of cytochrome P450 1A2 remarkably enhance homolytic O-O cleavage of alkyl hydroperoxides. An optical absorption spectral study. J Biol Chem 269:13296–13304.
  • Shimizu, T., Sadeque, A. J., Hatano, M., Fujii-Kuriyama, Y. (1989). Bindings of axial ligands to cytochrome P450d mutants: a difference absorption spectral study. Biochim Biophys Acta 995:116–121.
  • Shimizu, T., Tateishi, T., Hatano, M., Fujii-Kuriyama, Y. (1991b). Probing the role of lysines and arginines in the catalytic function of cytochrome P450d by site-directed mutagenesis. Interaction with NADPH-cytochrome P450 reductase. J Biol Chem 266:3372–3375.
  • Shimizu, Y., Nakatsuru, Y., Ichinose, M., Takahashi, Y., Kume, H., Mimura, J., et al. (2000). Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A 97:779–782.
  • Shimoda, K., Someya, T., Morita, S., Hirokane, G., Yokono, A., Takahashi, S., et al. (2002). 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.
  • 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.
  • Shou, M., Gonzalez, F. J., Gelboin, H. V. (1996a). Stereoselective epoxidation and hydration at the K-region of polycyclic aromatic hydrocarbons by cDNA-expressed cytochromes P450 1A1, 1A2, and epoxide hydrolase. Biochemistry 35:15807–15813.
  • Shou, M., Krausz, K. W., Gonzalez, F. J., Gelboin, H. V. (1996b). Metabolic activation of the potent carcinogen dibenzo[a,h]anthracene by cDNA-expressed human cytochromes P450. Arch Biochem Biophys 328:201–207.
  • Siess, M. H., Leclerc, J., Canivenc-Lavier, M. C., Rat, P., Suschetet, M. (1995). Heterogenous effects of natural flavonoids on monooxygenase activities in human and rat liver microsomes. Toxicol Appl Pharmacol 130:73–78.
  • Siller, M., Anzenbacher, P., Anzenbacherova, E., Dolezal, K., Popa, I., Strnad, M. (2009). Interactions of olomoucine II with human liver microsomal cytochromes P450. Drug Metab Dispos 37:1198–1202.
  • Silva, I. D., Rodrigues, A. S., Gaspar, J., Laires, A., Rueff, J. (1997). Metabolism of galangin by rat cytochromes P450: relevance to the genotoxicity of galangin. Mutat Res 393:247–257.
  • Silverman, E., Mouy, R., Spiegel, L., Jung, L. K., Saurenmann, R. K., Lahdenne, P., et al. (2005). Leflunomide or methotrexate for juvenile rheumatoid arthritis. N Engl J Med 352:1655–1666.
  • Sinclair, P. R., Gorman, N., Tsyrlov, I. B., Fuhr, U., Walton, H. S., Sinclair, J. F. (1998). Uroporphyrinogen oxidation catalyzed by human cytochromes P450. Drug Metab Dispos 26:1019–1025.
  • Skarke, C., Kirchhof, A., Geisslinger, G., Lotsch, J. (2005). Rapid genotyping for relevant CYP1A2 alleles by pyrosequencing. Eur J Clin Pharmacol 61:887–892.
  • Skene, D. J., Papagiannidou, E., Hashemi, E., Snelling, J., Lewis, D. F., Fernandez, M., et al. (2001). Contribution of CYP1A2 in the hepatic metabolism of melatonin: studies with isolated microsomal preparations and liver slices. J Pineal Res 31:333–342.
  • Slaughter, D., Takenaga, N., Lu, P., Assang, C., Walsh, D. J., Arison, B. H., et al. (2003). Metabolism of rofecoxib in vitro using human liver subcellular fractions. Drug Metab Dispos 31:1398–1408.
  • Smith, A. G., Davies, R., Dalton, T. P., Miller, M. L., Judah, D., Riley, J., et al. (2003). Intrinsic hepatic phenotype associated with the Cyp1a2 gene as shown by cDNA expression microarray analysis of the knockout mouse. EHP Toxicogenomics 111:45–51.
  • Solus, J. F., Arietta, B. J., Harris, J. R., Sexton, D. P., Steward, J. Q., McMunn, C., et al. (2004). Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics 5:895–931.
  • Somers, G. I., Harris, A. J., Bayliss, M. K., Houston, J. B. (2007). The metabolism of the 5-HT3 antagonists ondansetron, alosetron and GR87442 I: a comparison of in vitro and in vivo metabolism and in vitro enzyme kinetics in rat, dog and human hepatocytes, microsomes and recombinant human enzymes. Xenobiotica 37:832–854.
  • Somerville, L. L. (2001). Theophylline revisited. Allergy Asthma Proc 22:347–351.
  • Song, J., Clagett-Dame, M., Peterson, R. E., Hahn, M. E., Westler, W. M., Sicinski, R. R., et al. (2002). A ligand for the aryl hydrocarbon receptor isolated from lung. Proc Natl Acad Sci U S A 99:14694–14699.
  • 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., Saito, Y., Hanioka, N., Maekawa, K., Komamura, K., Kamakura, S., et al. (2005). Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population. Drug Metab Pharmacokinet 20:24–33.
  • 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.
  • Springer, D., Paul, L. D., Staack, R. F., Kraemer, T., Maurer, H. H. (2003). Identification of cytochrome P450 enzymes involved in the metabolism of 4’-methyl-α-pyrrolidinopropiophenone, a novel scheduled designer drug, in human liver microsomes. Drug Metab Dispos 31:979–982.
  • Stevens, C. W., Manoharan, T. H., Fahl, W. E. (1988). Characterization of mutagen-activated cellular oncogenes that confer anchorage independence to human fibroblasts and tumorigenicity to NIH 3T3 cells: sequence analysis of an enzymatically amplified mutant HRAS allele. Proc Natl Acad Sci U S A 85:3875–3879.
  • Stiborova, M., Frei, E., Breuer, A., Wiessler, M., Schmeiser, H. H. (2001a). Evidence for reductive activation of carcinogenic aristolochic acids by prostaglandin H synthase — 32P-postlabeling analysis of DNA adduct formation. Mutat Res 493:149–160.
  • Stiborova, M., Frei, E., Sopko, B., Wiessler, M., Schmeiser, H. H. (2002a). Carcinogenic aristolochic acids upon activation by DT-diaphorase form adducts found in DNA of patients with Chinese herbs nephropathy. Carcinogenesis 23:617–625.
  • Stiborova, M., Frei, E., Wiessler, M., Schmeiser, H. H. (2001b). Human enzymes involved in the metabolic activation of carcinogenic aristolochic acids: evidence for reductive activation by cytochromes P450 1A1 and 1A2. Chem Res Toxicol 14:1128–1137.
  • Stiborova, M., Martinek, V., Rydlova, H., Hodek, P., Frei, E. (2002b). Sudan I is a potential carcinogen for humans: evidence for its metabolic activation and detoxication by human recombinant cytochrome P450 1A1 and liver microsomes. Cancer Res 62:5678–5684.
  • Stormer, E., von Moltke, L. L., Shader, R. I., Greenblatt, D. J. (2000). Metabolism of the antidepressant mirtazapine in vitro: contribution of cytochromes P450 1A2, 2D6, and 3A4. Drug Metab Dispos 28:1168–1175.
  • 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.
  • Strushkevich, N., Usanov, S. A., Plotnikov, A. N., Jones, G., Park, H. W. (2008). Structural analysis of CYP2R1 in complex with vitamin D3. J MolBiol 380:95–106.
  • Sugahara, H., Maebara, C., Ohtani, H., Handa, M., Ando, K., Mine, K., et al. (2009). Effect of smoking and CYP2D6 polymorphisms on the extent of fluvoxamine-alprazolam interaction in patients with psychosomatic disease. Eur J Clin Pharmacol 65:699–704.
  • Suzuki, H., Morris, J. S., Li, Y., Doll, M. A., Hein, D. W., Liu, J., et al. (2008). Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis 29:1184–1191.
  • Takagi, S., Nakajima, M., Mohri, T., Yokoi, T. (2008). Post-transcriptional regulation of human pregnane X receptor by micro-RNA affects the expression of cytochrome P450 3A4. J Biol Chem 283:9674–9680.
  • Takata, K., Saruwatari, J., Nakada, N., Nakagawa, M., Fukuda, K., Tanaka, F., et al. (2006). Phenotype-genotype analysis of CYP1A2 in Japanese patients receiving oral theophylline therapy. Eur J Clin Pharmacol 62:23–28.
  • Tantcheva-Poor, I., Zaigler, M., Rietbrock, S., Fuhr, U. (1999). Estimation of cytochrome P450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics 9:131–144.
  • Tarrus, E., Cami, J., Roberts, D. J., Spickett, R. G., Celdran, E., Segura, J. (1987). Accumulation of caffeine in healthy volunteers treated with furafylline. Br J Clin Pharmacol 23:9–18.
  • Tassaneeyakul, W., Birkett, D. J., McManus, M. E., Tassaneeyakul, W., Veronese, M. E., Andersson, T., et al. (1994). Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Biochem Pharmacol 47:1767–1776.
  • Tassaneeyakul, W., Birkett, D. J., Veronese, M. E., McManus, M. E., Tukey, R. H., Quattrochi, L. C., et al. (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., et al. (1992). Caffeine as a probe for human cytochromes P450: validation using cDNA-expression, immunoinhibition and microsomal kinetic and inhibitor techniques. Pharmacogenetics 2:173–183.
  • 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.
  • Teo, S. K., Sabourin, P. J., O’Brien, K., Kook, K. A., Thomas, S. D. (2000). Metabolism of thalidomide in human microsomes, cloned human cytochrome P-450 isozymes, and Hansen’s disease patients. J Biochem Mol Toxicol 14:140–147.
  • Thelingwani, R. S., Zvada, S. P., Dolgos, H., Ungell, A. L., Masimirembwa, C. M. (2009). In vitro and in silico identification and characterization of thiabendazole as a mechanism-based inhibitor of CYP1A2 and simulation of possible pharmacokinetic drug-drug interactions. Drug Metab Dispos 37:1286–1294.
  • Thijssen, H. H., Flinois, J. P., Beaune, P. H. (2000). Cytochrome P4502C9 is the principal catalyst of racemic acenocoumarol hydroxylation reactions inhuman liver microsomes. Drug Metab Dispos 28:1284–1290.
  • Tjia, J. F., Colbert, J., Back, D. J. (1996). Theophylline metabolism in human liver microsomes: inhibition studies. J Pharmacol Exp Ther 276:912–917.
  • Tolleson, W. H., Doerge, D. R., Churchwell, M. I., Marques, M. M., Roberts, D. W. (2002). Metabolism of biochanin A and formononetin by human liver microsomes in vitro. J Agric Food Chem 50:4783–4790.
  • Topol, E. J. (2004). Failing the public health - rofecoxib, Merck, and the FDA. N Engl J Med 351:1707–1709.
  • Tsuchiya, Y., Nakajima, M., Takagi, S., Taniya, T., Yokoi, T. (2006). MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res 66:9090–9098.
  • Tsuneoka, Y., Dalton, T. P., Miller, M. L., Clay, C. D., Shertzer, H. G., Talaska, G., et al. (2003). 4-Aminobiphenyl-induced liver and urinary bladder DNA adduct formation in CYP1A2−/−and CYP1A2+/+ mice. J Natl Cancer Inst 95:1227–1237.
  • Tsyrlov, I. B., Mikhailenko, V. M., Gelboin, H. V. (1994). Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P450s to different flavonoids. Biochim Biophys Acta 1205:325–335.
  • Tuck, S. F., Hiroya, K., Shimizu, T., Hatano, M., Ortiz de Montellano P. R. (1993). The cytochrome P450 1A2 active site: topology and perturbations caused by glutamic acid-318 and threonine-319 mutations. Biochemistry 32:2548–2553.
  • Tucker, G. T., Lennard, M. S., Ellis, S. W., Woods, H. F., Cho, A. K., Lin, L. Y., et al. (1994). The demethylenation of methylenedioxymethamphetamine (“ecstasy”) by debrisoquine hydro xylase (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., Constable, A., Richoz, J., Varga, N., Markovic, J., Martin, M. V., et al. (1998). Activation of heterocyclic aromatic amines by rat and human liver microsomes and by purified rat and human cytochrome P450 1A2. Chem Res Toxicol 11:925–936.
  • Turesky, R. J., Guengerich, F. P., Guillouzo, A., Langouet, S. (2002a). Metabolism of heterocyclic aromatic amines by human hepatocytes and cytochrome P450 1A2. MutatRes 506-507:187–195.
  • Turpeinen, M., Hofmann, U., Klein, K., Murdter, T., Schwab, M., Zanger, U. M. (2009). A predominate role of CYP1A2 for the metabolism of nabumetone to the active metabolite, 6-methoxy-2-naphthylacetic acid, in human liver microsomes. Drug Metab Dispos 37:1017–1024.
  • Uckun, F. M., Thoen, J., Chen, H., Sudbeck, E., Mao, C., Malaviya, R., et al. (2002). CYP1A-mediated metabolism of the Janus kinase-3 inhibitor 4-(4’-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline: structural basis for inactivation by regioselective O-demethylation. Drug Metab Dispos 30:74–85.
  • Ueda, R., Iketaki, H., Nagata, K., Kimura, S., Gonzalez, F. J., Kusano, K., et al. (2006). A common regulatory region functions bidirectionally in transcriptional activation of the human CYP1A1 and CYP1A2 genes. Mol Pharmacol 69:1924–1930.
  • Ueng, Y. F., Hsieh, C. H., Don, M. J., Chi, C. W., Ho, L. K. (2004). Identification of the main human cytochrome P450 enzymes involved in safrole 1’-hydroxylation. Chem Res Toxicol 17:1151–1156.
  • Ueng, Y. F., Jan, W. C., Lin, L. C., Chen, T. L., Guengerich, F. P., Chen, C. F. (2002). The alkaloid rutaecarpine is a selective inhibitor of cytochrome P450 1A in mouse and human liver microsomes. Drug Metab Dispos 30:349–353.
  • 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.
  • Urban, P., Jobert, A. S., Laine, R., Pompon, D. (2001). Cytochrome P450 (CYP) mutants and substrate-specificity alterations: segment-directed mutagenesis applied to human CYP1A1. Biochem Soc Trans 29:128–135.
  • 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)1 A2. J Endocrinol Invest 26:403–406.
  • 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.
  • Van Cantfort J., Goujon, F. M., Gielen, J. E. (1979). Benzo[a]pyrene metabolism in rat fetal hepatocytes culture. Improved methodology and effect of substrate concentration. Chem Biol Interact 28:147–160.
  • van der Weide J., Steijns, L. S., van Weelden M. J. (2003). The effect of smoking and cytochrome P450 CYP1A2 genetic polymorphism on clozapine clearance and dose requirement. Pharmacogenetics 13:169–172.
  • 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 Roon, E. N., Jansen, T. L., van de Laar, M. A., Janssen, M., Yska, J. P., Keuper, R., et al. (2005). Therapeutic drug monitoring of A771726, the active metabolite of leflunomide: serum concentrations predict response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis 64:569–574.
  • Vanherweghem, J. L., Depierreux, M., Tielemans, C., Abramowicz, D., Dratwa, M., Jadoul, M., et al. (1993). Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet 341:387–391.
  • Vasanthanathan, P., Hritz, J., Taboureau, O., Olsen, L., Jorgensen, F. S., Vermeulen, N. P., et al. (2009a). Virtual screening and prediction of site of metabolism for cytochrome P450 1A2 ligands. J Chem Inf Model 49:43–52.
  • Vasanthanathan, P., Taboureau, O., Oostenbrink, C., Vermeulen, N. P., Olsen, L., Jorgensen, F. S. (2009b). Classification of cytochrome P450 1A2 inhibitors and noninhibitors by machine learning techniques. Drug Metab Dispos 37:658–664.
  • Vaziri, S. A., Hughes, N. C., Sampson, H., Darlington, G., Jewett, M. A., Grant, D. M. (2001). Variation in enzymes of arylamine procarcinogen biotransformation among bladder cancer patients and control subjects. Pharmacogenetics 11:7–20.
  • Venkatakrishnan, K., Schmider, J., Harmatz, J. S., Ehrenberg, B. L., von Moltke, L. L., Graf, J. A., et al. (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., 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.
  • Vickers, A. E., Sinclair, J. R., Zollinger, M., Heitz, F., Glanzel, U., Johanson, L., et al. (1999). Multiple cytochrome P450s involved in the metabolism of terbinafine suggest a limited potential for drug-drug interactions. Drug Metab Dispos 27:1029–1038.
  • von Moltke, L. L., Greenblatt, D. J., Duan, S. X., Schmider, J., Kudchadker, L., Fogelman, S. M., et al. (1996). Phenacetin O-deethylation by human liver microsomes in vitro: inhibition by chemical probes, SSRI antidepressants, nefazodone and venlafaxine. Psychopharmacology (Berl) 128:398–407.
  • Von Richter, O., Lahu, G., Huennemeyer, A., Herzog, R., Zech, K., Hermann, R. (2007). Effect of fluvoxamine on the pharmacokinetics of roflumilast and roflumilast N-oxide. Clin Pharmacokinet 46:613–622.
  • Wang, B., Zhou, S. F. (2009). Synthetic and natural compounds that interact with human cytochrome P450 1A2 and implications in drug development. Curr Med Chem 16:4066–4218.
  • 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, Z., Gorski, J. C., Hamman, M. A., Huang, S. M., Lesko, L. J., Hall, S. D. (2001). The effects of St John’s wort (Hypericum perforatum) on human cytochrome P450 activity. Clin Pharmacol Ther 70:317–326.
  • 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.
  • Waxman, D. J., Chang, T. K. (2006). Use of 7-ethoxycoumarin to monitor multiple enzymes in the human CYP1, CYP2, and CYP3 families. Methods Mol Biol 320:153–156.
  • Weinberger, M., Hendeles, L. (1996). Theophylline in asthma. N Engl J Med 334:1380–1388.
  • 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, X., Wang, J. S., Neuvonen, P. J., Backman, J. T. (2002). Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes. Eur J Clin Pharmacol 57:799–804.
  • Wenzlaff, A. S., Cote, M. L., Bock, C. H., Land, S. J., Santer, S. K., Schwartz, D. R., et al. (2005). CYP1A1 and CYP1B1 polymorphisms and risk of lung cancer among never smokers: a population-based study. Carcinogenesis 26:2207–2212.
  • Wester, M. R., Yano, J. K., Schoch, G. A., Yang, C., Griffin, K. J., Stout, C. D., et al. (2004). The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-Å resolution. J Biol Chem 279:35630–35637.
  • Wetzel, H., Anghelescu, I., Szegedi, A., Wiesner, J., Weigmann, H., Harter, S., et al. (1998). Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol 18:2–9.
  • 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.
  • 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.
  • Williams, P. A., Cosme, J., Vinkovic, D. M., Ward, A., Angove, H. C., Day, P. J., et al. (2004). Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 305:683–686.
  • Williams, P. A., Cosme, J., Ward, A., Angove, H. C., Matak Vinkovic, D., Jhoti, H. (2003). Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 424:464–468.
  • Winter, J., Jung, S., Keller, S., Gregory, R. I., Diederichs, S. (2009). Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11:228–234.
  • Wiseman, R. W., Miller, E. C., Miller, J. A., Liem, A. (1987). Structure-activity studies of the hepatocarcinogenicities of alkenylbenzene derivatives related to estragole and safrole on administration to preweanling male C57BL/6J × C3H/HeJ F1 mice. Cancer Res 47:2275–2283.
  • Wislocki, P. G., Borchert, P., Miller, J. A., Miller, E. C. (1976). The metabolic activation of the carcinogen 1 ‘-hydroxysafrole in vivo and in vitro and the electrophilic reactivities of possible ultimate carcinogens. Cancer Res 36:1686–1695.
  • Wislocki, P. G., Miller, E. C., Miller, J. A., McCoy, E. C., Rosenkranz, H. S. (1977). Carcinogenic and mutagenic activities of safrole, 1’-hydroxysafrole, and some known or possible metabolites. Cancer Res 37:1883–1891.
  • 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.
  • Wolkenstein, P., Tan, C., Lecoeur, S., Wechsler, J., Garcia-Martin, N., Charue, D., et al. (1998). Covalent binding of carbamazepine reactive metabolites to P450 isoforms present in the skin. Chem Biol Interact 113:39–50.
  • Woo, S. W., Kang, T. S., Park, H. J., Lee, J. E., Roh, J. (2009). Comparison of linkage disequilibrium patterns and haplotype structure of eight single nucleotide polymorphisms across the CYP1A2 gene between the Korean, and other populations registered in the International HapMap database. J Clin Pharm Ther 34:429–436.
  • Wooding, S. P., Watkins, W. S., Bamshad, M. J., Dunn, D. M., Weiss, R. B., Jorde, L. B. (2002). DNA sequence variation in a 3.7-kb noncoding sequence 5’ of the CYP1A2 gene: implications for human population history and natural selection. Am J Hum Genet 71:528–542.
  • Wray, G. A., Hahn, M. W., Abouheif, E., Balhoff, J. P., Pizer, M., Rockman, M. V., et al. (2003). The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol 20:1377–1419.
  • 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.
  • Xiao, C., Rajewsky, K. (2009). MicroRNA control in the immune system: basic principles. Cell 136:26–36.
  • Yamazaki, H., Guo, Z., Persmark, M., Mimura, M., Inoue, K., Guengerich, F. P., et al. (1994). Bufuralol hydroxylation by cytochrome P450 2D6 and 1A2 enzymes in human liver microsomes. Mol Pharmacol 46:568–577.
  • Yamazaki, H., Inoue, K., Hashimoto, M., Shimada, T. (1999). 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 inhuman liver microsomes. Biochem Pharmacol 51:313–319.
  • Yamazaki, H., Inoue, K., Shaw, P. M., Checovich, W. J., Guengerich, F. P., Shimada, T. (1997). Different contributions of cytochrome P450 2C19 and 3A4 in the oxidation of omeprazole by human liver microsomes: effects of contents of these two forms in individual human samples. J Pharmacol Exp Ther 283:434–442.
  • Yamazaki, H., Shaw, P. M., Guengerich, F. P., Shimada, T. (1998). Roles of cytochromes P450 1A2 and 3A4 in the oxidation of estradiol and estrone in human liver microsomes. Chem Res Toxicol 11:659–665.
  • Yanagita, K., Sagami, I., Daff, S., Shimizu, T. (1998). Marked enhancement in the reductive dehalogenation of hexachloroethane by a Thr319Ala mutation of cytochrome P450 1A2. Biochem Biophys Res Commun 249:678–682.
  • 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.
  • 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.
  • Yano, J. K., Wester, M. R., Schoch, G. A., Griffin, K. J., Stout, C. D., Johnson, E. F. (2004). The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-Å resolution. J Biol Chem 279:38091–38094.
  • Yao, C., Kunze, K. L., Trager, W. F., Kharasch, E. D., Levy, R. H. (2003). Comparison of in vitro and in vivo inhibition potencies of fluvoxamine toward CYP2C19. Drug Metab Dispos 31:565–571.
  • Yasuda, T., Kon, R., Nakazawa, T., Ohsawa, K. (1999). Metabolism of paeonol in rats. J Nat Prod 62:1142–1144.
  • Yeh, R. F., Gaver, V. E., Patterson, K. B., Rezk, N. L., Baxter-Meheux, F., Blake, M. J., et al. (2006). Lopinavir/ritonavir induces the hepatic activity of cytochrome P450 enzymes CYP2C9, CYP2C19, and CYP1A2 but inhibits the hepatic and intestinal activity of CYP3A as measured by a phenotyping drug cocktail in healthy volunteers. J Acquir Immune Defic Syndr 42:52–60.
  • Yew, W. W. (2002). Clinically significant interactions with drugs used in the treatment of tuberculosis. Drug Safety 25:111–133.
  • Yoshinari, K., Ueda, R., Kusano, K., Yoshimura, T., Nagata, K., Yamazoe, Y. (2008). Omeprazole transactivates human CYP1A1 and CYP1A2 expression through the common regulatory region containing multiple xenobiotic-responsive elements. Biochem Pharmacol 76:139–145.
  • Yuan, J. M., Chan, K. K., Coetzee, G. A., Castelao, J. E., Watson, M. A., Bell, D. A., et al. (2008). Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer. Carcinogenesis 29:1386–1393.
  • 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.
  • Yueh, M. F., Huang, Y. H., Hiller, A., Chen, S., Nguyen, N., Tukey, R. H. (2003). Involvement of the xenobiotic response element (XRE) in Ah receptor-mediated induction of human UDP-glucuronosyltransferase 1A1. J Biol Chem 278:15001–15006.
  • Yueh, M. F., Nguyen, N., Famourzadeh, M., Strassburg, C. P., Oda, Y., Guengerich, F. P., et al. (2001). The contribution of UDP-glucuronosyltransferase 1A9 on CYP1A2-mediated genotoxicity by aromatic and heterocyclic amines. Carcinogenesis 22:943–950.
  • Yun, C. H., Miller, G. P., Guengerich, F. P. (2000). Rate-determining steps in phenacetin oxidations by human cytochrome P450 1A2 and selected mutants. Biochemistry 39:11319–11329.
  • Yun, C. H., Miller, G. P., Guengerich, F. P. (2001). Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2: structure-activity relationships and simulation of rate constants of individual steps in catalysis. Biochemistry 40:4521–4530.
  • Yun, C. H., Shimada, T., Guengerich, F. P. (1992). Roles of human liver cytochrome P4502C and 3A enzymes in the 3-hydroxylation of benzo(a)pyrene. Cancer Res 52:1868–1874.
  • Zaccaro, C., Sweitzer, S., Pipino, S., Gorman, N., Sinclair, P. R., Sinclair, J. F., et al. (2001). Role of cytochrome P450 1A2 in bilirubin degradation studies in CYP1A2−/− mutant mice. Biochem Pharmacol 61:843–849.
  • Zevin, S., Benowitz, N. L. (1999). Drug interactions with tobacco smoking. An update. Clin Pharmacokinet 36:425–438.
  • 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.
  • Zhai, S., Dai, R., Friedman, F. K., Vestal, R. E. (1998a). Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids. Drug Metab Dispos 26:989–992.
  • Zhai, S., Dai, R., Wei, X., Friedman, F. K., Vestal, R. E. (1998b). Inhibition of methoxyresorufin demethylase activity by flavonoids in human liver microsomes. Life Sci 63:PL119-123.
  • Zhang, L., Wei, M. J., Zhao, C. Y., Qi, H. M. (2008). Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes. Acta Pharmacol Sin 29:1507–1514.
  • Zhang, Q. Y., Dunbar, D., Kaminsky, L. (2000). Human cytochrome P450 metabolism of retinals to retinoic acids. Drug Metab Dispos 28:292–297.
  • Zhang, Z. Y., Kaminsky, L. S. (1995). Characterization of human cytochromes P450 involved in theophylline 8-hydroxylation. Biochem Pharmacol 50:205–211.
  • Zheng, Y. M., Henne, K. R., Charmley, P., Kim, R. B., McCarver, D. G., Cabacungan, E. T., et al. (2003). Genotyping and site-directed mutagenesis of a cytochrome P450 meander Pro-X-Arg motif critical to CYP4B1 catalysis. Toxicol Appl Pharmacol 186:119–126.
  • Zhou, H., Josephy, P. D., Kim, D., Guengerich, F. P. (2004a). Functional characterization of four allelic variants of human cytochrome P450 1A2. Arch Biochem Biophys 422:23–30.
  • Zhou, S., Chan, E., Li, X., Huang, M. (2005a). Clinical outcomes and management of mechanism-based inhibition of cytochrome P450 3A4. Ther Clin Risk Manag 1:3–13.
  • Zhou, S., Chan, E., Lim, L. Y., Boelsterli, U. A., Li, S. C., Wang, J., et al. (2004b). Therapeutic drugs that behave as mechanism-based inhibitors of cytochrome P450 3A4. Curr Drug Metab 5:415–442.
  • Zhou, S., Gao, Y., Jiang, W., Huang, M., Xu, A., Paxton, J. W. (2003). Interactions of herbs with cytochrome P450. Drug Metab Rev 35:35–98.
  • 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., Yung Chan, S. Cher, Goh, B., Chan, E., Duan, W., Huang, M. et, al. (2005b). Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet 44:279–304.
  • Zhou, S. F., Chan, E., Zhou, Z. W., Xue, C. C., Lai, X., Duan, W. (2009a). Insights into the structure, function, and regulation of human cytochrome P450 1A2. Curr Drug Metab 10:713–729.
  • Zhou, S. F., Di, Y. M., Chan, E., Du, Y. M., Chow, V. D., Xue, C. C., et al. (2008). Clinical pharmacogenetics and potential application in personalized medicine. Curr Drug Metab 9:738–784.
  • Zhou, S. F., Koh, H. L., Gao, Y. H., Gong, Z. Y., Lee, E. J. D. (2004c). Herbal bioactivation: the good, the bad and the ugly. Life Sci 74:935–968.
  • Zhou, S. F., Lai, X. (2008). An update on clinical drug interactions with the herbal antidepressant St John’s wort. Curr Drug Metab 9:394–409.
  • Zhou, S. F., Liu, J. P., Chowbay, B. (2009b). Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metab Rev 41:89–295.
  • Zhou, S. F., Liu, Y. H., Mo, S. L., Chan, E. (2009c). Insights into the substrate specificity, inhibitors, and polymorphism and the clinical impact of human cytochrome P450 1A2. AAPS J 11:481–494.
  • Zhou, S. F., Xue, C. C., Yu, X. Q., Li, C., Wang, G. (2007a). Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring. Ther Drug Monit 29:687–710.
  • Zhou, S. F., Xue, C. C., Yu, X. Q., Wang, G. (2007b). Metabolic activation of herbal and dietary constituents and its clinical and toxicological implications: an update. Curr Drug Metab 8:526–553.
  • Zhou, Z. W., Zhou, S. F. (2009). Application of mechanism-based CYP inhibition for predicting drug-drug interactions. Expert Opin Drug Metab Toxicol 5:579–605.
  • Zhu, Q., Liao, J., Xie, L., Wang, G. J., Liu, X. D. (2009). Mechanism-based inhibition of CYP1A2 by antofloxacin, an 8-NH2 derivative of levofloxacin in rats. Xenobiotica 39:293–301.

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