Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 28, 1998 - Issue 12
183
Views
81
CrossRef citations to date
0
Altmetric
Research Article

Human cytochrome P450s: selectivity and measurement in vivo

, , &
Pages 1095-1128 | Published online: 22 Sep 2008

Reference

  • ABEL, S. M., MAGGS, J. L., BACK, D. J. and PARK, B. K., 1991, Cortisol metabolism by human liver in vitro—I. Metabolite Identification and inter-individual v ariability journal of Steroid Biochemistry and Molecular Biology, 43, 713–719.
  • AHONEN, J., OLKKOLA, K. T. and NEUVONEN, P. J., 1995, Effects of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. British Journal of Clinical Pharmacology, 40, 270–272.
  • AL-HADIDI, H. F., IRSHAID, Y. M. and RAWASHDEH, N. M., 1994, Metoprolol a-hydroxylation is a poor probe for debrizoquine oxidation (CYP2D6) polymorphism in Jordanians. European Journal of Clinical Pharmacology, 47, 311–314.
  • ALVAN, G., BECHTEL, B., 'sums, L. and GUNDERT -REMY, U., 1990, Hydroxylation polymorphism of debrisoquine and mephenytoin in European populations. European Journal of Clinical Phar-macology, 39, 533–537.
  • ANDERSSON T., 1991, Omeprazole drug interaction studies. Clinical Pharmacokinetics, 21, 195-212. ANDERSSON, T., MINERS, J. 0., VERONSE, M. E. and BIRKETT, D. J., 1994, Diazepam metabolism by human liver microsomes is mediated by both (S)-mephenytoin hydroxylase and CYP3A isoforms. British Journal of Clinical Pharmacology, 38, 131–137.
  • ANDERSSON, T., REGARDH, C. G., Lou, Y. C., ZHANG, Y., DAHL, ML. and BERTILSSON, L., 1992, Polymorphic hydroxylation of (S)-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects. Pharmacogenetics, 2, 25–31.
  • ANGELO, M., DRING, L. G., LANCASTER, R., LATHAM, A. and SMITH, R. L., 1975, A correlation between the response to debrisoquine and the amount of unchanged drug excreted in the urine. British Journal of Pharmacology, 55, 264P.
  • AOYAMA, T., YAMANO, S., WAXMAN, D. J., LAPENSON, D. P., MEYER, U. A., FISCHER, V., TYNDALE, R., INABA, T., KALOW, W., GELBOIN, H. V. and GONZALEZ, F. J., 1989, Cytochrome P-450 hPCN3, a novel cytochrome P-450IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporin. Journal of Biological Chemistry, 264, 10388–10395.
  • BACK, D. J. and TEA, J. F., 1991, Comparative effects of the antimycotic drugs ketoconazole, fluconazole, itraconazole and terbinafine on the metabolism of cyclosporing by human liver microsomes. British Journal of Clinical Pharmacology, 32, 5,624–6.
  • BERTILSSON, L., 1995, Geographical/interracial differences in polymorphic drug oxidation. Clinical Pharmacokinetic Concepts, 29, 192–209.
  • BERTILSSON, L., CARRILLO, J. A., DAHL, M. L., LLERENA, A., ALM, C., BONDESSON, U., LINDSTROM, L.,
  • RODRIGUEZ -DE-LA-RUBIA, I., RAMOS, S. and BENITEZ, J., 1994, Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. British Journal of Clinical Pharmacology, 38, 471–473.
  • BERTILSSON, L., HENTHRON, T. K., SANZ, E., TYBRING, G., SAWE, J. and VILLEN, T., 1989, Importance of genetic factors in the regulation of diazepam metabolism: relationship to (S)-mephenyto in, but not debrisoquine, hydroxylation phenotype. Clinical Pharmacology and Therapeutics, 45, 348–355.
  • BLYCHERT, E., EDGAR, B., ELMFELDT, D. and HEDNER, T., 1991, A population study of the pharmacokinetics of felodipine. British Journal of Clinical Pharmacology, 31, 15–24.
  • BOOBIS, A. R., LYNCH, AM., MURRAY, S., DE LA TORRE, R., SOLANS, A., FARRE, M., SEGURA, J., GOODERHAM, N. J. and DAVIES, D. S., 1994, CYP1A2 catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Cancer Research, 54, 89–94.
  • BOZKURT, A., BASCI, N. E., IsEsnEK, A., SAYAL, A. and KAYAALP, SO., 1994, Polymorphic debrisoquin metabolism in a Turkish population. Clinical Pharmacology and Therapeutics, 55, 399–401.
  • BREYER-PFAFF, U., PFANDL, B., NILL, K., NUSSER, E., MONNEY, C., JONZ1ER -PEREY, M., BAETTIG, D. and BAUMANN, P., 1992, Enantioselective amitriptyline metabolism in patients phenotyped for two cytochrome P450 isozymes. Clinical Pharmacology and Therapeutics, 52, 350–358.
  • BROGDEN, R. N., HL, R. C., SPEIGHT, T. M. and AVERY, G. S., 1979, Naproxden up to date: A review of its pharmacological properties and therapeutic efficacy and use in rheumatic diseases and pain states. Drugs, 18, 241–277.
  • BROSEN, K., ZEUGIN, T. and MEYER, U. A., 1992, Role of P450IID6, the target of the sparteine-debrisoquin oxidation polymorphism, in the metabolism of imipramine. Clinical Pharmacology and Therapeutics, 49, 609–617.
  • BUTLER, M. A., IWASAKI, M., GUENGERICH, F. P. and KADLUBAR, F. F., 1989, Human cytochrome P450PA (P450IA2), the phenacetin 0-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proceedings of the National Academy of Sciences, USA, 86, 7696–7700.
  • CAMPBELL, M. E., SPEILBERG, S. P. and KALO W., 1987, A urinary metabolite ratio that reflects systemic caffeine clearance. Clinical Pharmacology and Therapeutics, 42, 157–165.
  • CARRIERE, V., GOASDUFF, T., RATANASAVANH, D., MOREL, F., GAUTIER, J.-C., GUILLOUZO, A., BEAUNE, P. and BERTHOU, F., 1993, Both cytochromes P450 2E1 and 1A1 are involved in the metabolism of chlorzoxazone. Chemical Research and Toxicology, 6, 852–857.
  • CATTEAU, A., BECHET, Y. C., POISSON, N., BETCHEL, P. R. and BONAITI -PELLIE, C., 1995, A population and family study of CYP1A2 using caffeine urinary metabolites. European Journal of Clinical Pharmacology, 47, 423–430.
  • CHIBA, K., KOBAYASHI, K., MANABE, K., TANI, M., KAMATAKI, T. and ISHIZAKI, T., 1993, Oxidative metabolism of omeprazole in human liver microsomes : cosegregation with (S)-mephenytoin 4"-hydroxylation. Journal of Pharmacology and Experimental Therapeutics, 266, 5323–59.
  • CHIBA, K., SAITOH, A., KOYAMA, E., TAM, M., HAYASHI, M. and ISHIZAKI, T., 1994, The role of (S)-mephenytoin 4'-hydroxylase in imipramine metabolism by human liver microsomes : a two-enzyme analysis of N-demethylation and 2-hydroxylation. British Journal of Clinical Phar-macology, 37, 237–242.
  • CLARKE, S. E., AYRTON, A. D. and CHENERY, R. J., 1994, Characterisation of the inhibition of 1A2 by furafylline. Xenobiotica, 24, 517–526.
  • CUPPY -VICKERY, J. R. and PouLos, T. L., 1995, Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Structural Biology, 2, 144–152.
  • CURI-PEDROSA, R., DAUJAT, M., PICHARD, L., OURLIN, J. C., CLAIR, P., GERVOT, L., LESCA, P., DOIVIERGUE, J., JoYEux, H., FOURTAN1ER, G. and MAUREL, P., 1994, Omeprazole and lansoprazole are mixed inducers of CYP1A and CYP3A in human hepatocytes in primary culture. Journal of Pharmacology and Experimental Therapeutics, 269, 384–392.
  • DAHL, M.-L., TYBRING, G., ELWIN, C.-E., ALM, C., ANDREASSON, K., GYLLENPALM, M. and BERTILSSON, L., 1994, Stereoselective disposition of mianserin is related to debrisoquin hydroxylation polymorphism. Clinical Pharmacology and Therapeutics, 56, 176–183.
  • DALY, A. K., CHOLERTON, S., GREGORY, W. and IDLE, J. R., 1993, Metabolic polymorphisms. Pharmacology and Therapeutics, 57, 129–160.
  • DANESHIVIEND, T. K. and WARNOCK, D. W., 1988, Clinical pharmacokinetics of ketoconazole. Clinical Pharmacokinetics, 14, 13–34.
  • DE LA FORGE, M., JAQUEN, M. and MANSUY, D., 1983, Dual effects of macrolide antibiotics On rat liver cytochrome P450. Induction and formation of metabolite complexes: a structure-activity relationship. Biochemical Pharmacology, 32, 2309–2318.
  • DE WAZ1ERS, I., CUGNENC, P. H., YANG, C. S., LEROUX J.-P. and BEAUNE, P. H., 1990, Cytochrome P450 Isoenzymes, epoxide hydrolase and glutathione transferase in rat and human hepatic and extrahepatic tissues. Journal of Pharmacology and Experimental Therapeutics, 253, 387–394. DICKERSON, R. G., HOOPER, W. D., PATTERSON, M., EAD1E, M. J. and MAGUIRE, B., 1985, Extent of urinary excretion of p-hydroxyphenytoin in healthy subjects given phenytoin. Therapeutic Drug Monitering, 7, 283–289.
  • DOECKE, C. J., VERONESE, M. E., POND, S. M., MINERS, J. 0., BIRKETT, D. J., SANSOM, L. N. and McMANus, M. E., 1991, Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes. British Journal of Clinical Pharmacology, 31, 124–130.
  • EADE, 0. E., MADDISON, A., LEONARD, P. J. and WRIGHT, R., 1977, Ratio of urinary 6fl-hydroxy-corticosteroids in patients with liver disease. Digestion, 16, 169–174.
  • EICHELBAUM, M., BERTILSSON, L., SAWE, J. and ZEKORN, C., 1982, Polymorphic oxidation of sparteine and debrisoquine: related pharmacogenetic entities. Clinical Pharmacology and Therapeutics, 31, 184–186.
  • EICHELBAUM, M. and GROSS, A. S., 1990, The genetic polymorphisms of debrisoquine/sparteine metabolism-clinical aspects. Pharmacology and Therapeutics, 46, 377–394.
  • EICHELBAUM, M., SPANNBRUCKER, N. and DENGLER, H. J., 1979b, Influence of the defective metabolism of sparteine on its pharmacokinetics. European Journal of Clinical Pharmacology, 16, 189–194.
  • EICHELBAUM, M., SPANNBRUCKER, N., STEINCKE, B. and DENGLER, H. J., 1979a, Defective N-oxidation of sparteine in man: a new pharmacogenetic defect. European Journal of Clinical Pharmacology, 16, 183–187.
  • ELLIS, S. W., HAYHURST, G. P., SMITH, G., LIGHTFOOT, T., WONG, M. M. S., SIMULA, A. P., ACKLAND M. J., S TERNBERG, M. J. E., LENNARD M. S., TUCKER, G. T. and WOLF, C. F., 1995, Evidence that aspartic acid 301 is a critical substrate-contact residue in the active site of cytochrome P450 2D6. Journal of Biological Chemistry, 270, 29055–29058.
  • EVANS, D. A. P., MAHGOUB, A., SLOAN, T. P., IDLE, J. R. and SMITH, R. L., 1980, A family and population study of genetic polymorphism of debrisoquine oxidation in a white British population. Journal of Medical Genetics, 17, 102–105.
  • EVANS, W. E. and RELLING, M. V., 1991, Concordance of P450 2D6 (debrisoquine hydroxylase) phenotype and genotype: inability of dextromethorphan metabolic ratio to discriminate reliably heterozygous and homozygous extensive metabolizers. Phamacogenetics, 1, 143–148.
  • FRANTZ, A. G., KATZ, F. H. and JAILER, J. W., 1960,6/3-hydroxycortisol: High levels in human urine in pregnancy and toxemia. Proceedings of the Society for Experimental Biology and Medicine, 105, 41–43.
  • FRIEDMAN, H., GREENBLATT, D. J. and BURSTEIN, E. S., 1986, Population study of triazolam pharmacokinetics. British Journal of Clinical Pharmacology, 22, 639–642.
  • GED, C., ROUILLON, M., PICHARD, L., COMBALBERT, J., BRESSOT, N., BORIES, P., MICHEL, H., BEAUNE, P. and MAUREL, P., 1989, The increase in urinary excretion of 6/3-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. British Journal of Clinical Pharmacology, 28, 373–387.
  • GERBER -TARAS, E., PARK, B. K. and OHNHAUS, E. E., 1981, The estimation of 6/3-hydroxycortisol in urine—a comparison of two methods: High performance liquid chromatography and radio-immunoassay. Journal of Clinical Chemistry and Clinical Biochemistry, 19, 525–527.
  • GIBSON, G. G. and TAMBURINI, P. P., 1984, Cytochrome P-450 spin state: inorganic biochemistry of haem iron ligation and functional significance. Xenobiotica, 14, 27–47.
  • GIRRE, C., LUCAS, D., HISPARD, E., MENEZ, C., DALLY, S. and MENEZ, J. F., 1994, Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics. Biochemical Pharmacology, 47, 1503–1508.
  • GOLDSTEIN, J. A., FALETTO, M. B., ROMKES -SPARKS, M., SULLIVAN, T., KITAREEWAN, S., RAUCY, J. L., LASKER, J. M. and GHANAYEM, B. I., 1994, Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans. Biochemistry, 33, 1743–1752.
  • GONZALEZ, F. J., 1992, Human cytochromes P450: problems and prospects. Trends in Pharmacological Sciences, 13, 346–352.
  • GONZALEZ, F. J., SKODA, R. C., KIMURA, S., UMENO, M., ZANGER, U. M., NEBERT, D. W., GELBOIN H. V., HARDWICK, J. P. and MEYER, U. A., 1988, Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature, 331, 442–446.
  • GOLDSTEIN, J. A. and DE MORMS, S. M. F., 1994, Biochemistry and molecular biology of the human CYP2C subfamily. Pharmacogenetics, 4, 285–299.
  • GUENGERICH, F. P. and MACDONALD, T. L., 1990, Mechanisms of cytochrome P450 catalysis. FASEB Journal, 4, 2453–2459.
  • GUT, J., CATIN, T., DAYER, P., KRONBACH, T., ZANGER, U. and MEYER, U. A., 1986, Debrisoquine/sparteine type polymorphism of drug oxidation. Journal of Biological Chemistry, 261, 11734–11743.
  • HARGREAVES, M. B., Jos, B. C., SMITH, D. A. and GESCHER, A., 1994, Inhibition of p-nitrophenol hydroxylase in rat liver microsomes by small aromatic and heterocyclic molecules. Drug Metabolism and Disposition, 22, 806–810.
  • HASEGAWA, T., HARA, K., KENMOCHI, T. and HATA, S., 1994, In vitro metabolism of dorzolamide, a novel potent carbonic anhydrase inhibitor, in rat liver microsomes. Drug Metabolism and Disposition, 22, 916–921.
  • HORSMAN, Y., DESAGER, J. P. and HARVENGT, C., 1992, Absence of CYP3A genetic polymorphism assessed by urinary excretion of 6/3-cortisol in 102 healthy subjects on rifampicin. Pharmacological Toxicology, 7, 258–261.
  • HOSODA, H., SAKAI, Y. and NAMBARA, T., 1981, A direct enzyme immunoassay of 6/3-hydroxycortisol in human urine. Chemistry and Pharmacology Bulletin (Tokyo), 29, 170–175.
  • HUNT, C. M., WATKINS, P. B., SAENGER ., P., STAVE, G. M., BARLASCINI, N., WATLINGTON, C. 0., WRIGHT, J. T. and GUZELIAN, P. S., 1992, Heterogeneity of CYP3A isoforms metabolizing erythromycin and cortisol. Clinical Pharmacology and Therapeutics, 51, 18–23.
  • INABA, T., JURIMA, M., MAHON, W. A. and KALO W., 1985, In vitro inhibition studies of two isozymes of human liver cytochrome P450, mephenytoin p-hydroxylase and sparteine monooxygenase. Drug Metabolism and Disposition, 13, 443–448.
  • INouE, S., INOKUMA, M., HARADA, T., SHIBUTANI, Y., YOSHITAKE, T., CHARLES, B., ISHIDA, J. and YAMAGUCHI, M., 1994, Simultaneous high performance liquid chromatographic determination of 6/3-hydroxycortisol and cortisol in urine with fluorescence detection and its application for estimating hepatic drug-metabolizing enzyme induction. Journal of Chromatography, 661,15–23.
  • IYUN, A. 0., LENNARD, M. S., TUCKER, G. T. and WOODS, H. F., 1986, Metoprolol and debrisoquin metabolism in Nigerians: lack of evidence for polymorphic oxidation. Clinical Pharmacology and Therapeutics, 40, 387–394.
  • JACKSON, P. R., TUCKER, G. T., LENNARD, M. S. and WOODS, H. F., 1986, Polymorphic drug oxidation: pharmacokinetic basis and comparison of experimental indices. British Journal of Clinical Pharmacology, 22, 541–550.
  • JONES, B. C., HAWKSWORTH, G., HORNE, V. A., NEWLANDS, A., MORSMAN, J., TUTE, M. S. and SMITH, D. A., 1996, Putative active site model for CYP2C9 (tolbutamide hydroxylase). Drug Metabolism and Disposition, 24, 1–7.
  • KALO W. and TANG, B.-K., 1993, The use of caffeine for enzyme assays: a critical appraisal. Clinical Pharmacology and Therapeutics, 53, 503–514.
  • KATZ, F. H., LIPMAN, M. M., FRANrz, A. G. and JAILOR, J. W., 1962, The physiologic significance of 6)3-hydroxycortisol in human cortisol metabolism. Journal of Clinical Endocrinology and Metabolism, 22, 71–77.
  • KHARASCH, E. D., THUMMEL, K. E., MAUTZ, D. and BOSSE, S., 1994, Clinical enflurane metabolism by cytochrome P4502E1. Clinical Pharmacology and Therapeutics, 55, 434–40.
  • KHARASCH, E. D., THUMMEL, K. E., MHYRE, J. and LILLIBRIDGE, J. H., 1993, Single dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1. Clinical Pharmacology and Therapeutics, 53, 643–650.
  • KIMURA, S., UMENO, M., SKODA, R. C., MEYER, U. A. and GONZALEZ, F. J., 1989, The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene and pseudogene. American Journal of Human Genetics, 45, 889–904.
  • KINIRONS, M. T., O'SHEA, D., DOWNING, T. E., FITZWILLIAM, A. T., JOELLENBECK, L., GROOPMAN J. D., WILKINSON, G. R. and WOOD, A. J. J., 1993, Absence of correlations among three putative in vivo probes of human cytochrome P4503A activity in young healthy men. Clinical Pharmacology and Therapeutics, 54, 621–629.
  • KOLARS, J. C., SCHMIEDLIN -REN, P., SCHUETZ, J. D., FANG, C. and WATKINS, P. B., 1992, Identification of rifampicin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. Journal of Clinical Investigation, 90, 1871–1878.
  • KOLEY, A. P., BUTTERS, J. T. M., ROBINSON, R. C., MARKOWITZ, A. and FRIEDMAN, F. K., 1995, CO Binding kinetics of human cytochrome P450 3A4. Journal of Biological Chemistry, 270, 5014–5018.
  • KONTAKE, A. N., SCHOELLER, D. A., LAMBERT, G. H., BAKER, A. L., SCHAFFER, D. D. and JOSEPHS, H., 1992, The caffeine CO2 breath test: dose response and route of N-demethylation in smokers and non-smokers. Clinical Pharmacology and Therapeutics, 32, 261–269.
  • KOOP, D. R., 1992, Oxidative and reductive metabolism by cytochrome P450 2E1. F ASEB Journal, 6, 724–730.
  • KORZEKWA, K. R. and JONES, J. P., 1993, Predicting the cytochrome P450 mediated metabolism of xenobiotics. Pharmacogenetics, 3, 1–18.
  • KOYAMA, E., SOHN, D.-R., SHIN, S.-G., CHIBA, K., SHIN, J.-G., KIM, Y.-H., ECHIZEN, H. and ISHIZAKI T., 1994, Metabolic disposition of imipramine in Oriental subjects: relation to metoprolol a-hydroxylation and S-mephenytoin C.-hydroxylation phenotypes. Journal of Pharmacology and Experimental Therapeutics, 271, 860–867.
  • KRIVORUK, Y., KINIRONS, M. T., WOOD, A. J. J. and WOOD, M., 1994, Metabolism of cytochrome P4503A substrates in vivo administered by the same route: lack of correlation between alfentanil clearance and erythromycin breath test. Clinical Pharmacology and Therapeutics, 56, 608–614.
  • KUNZE, K. L. and TRAGER, W. F., 1993, Isoform selective mechanism based inhibition of human cytochrome P4501A2 by furafylline. Chemical Research in Toxicology, 6, 649–656.
  • KUPFER, A., SCHMID, B. and PFAFF, G., 1986, Pharmacogenetics of dextromethorphan 0-demethylation in man. Xenobiotica, 16, 421–433.
  • LEE, C., 1995, Urinary 6/3-hydroxycortisol in humans: analysis, biological variations, and reference ranges. Clinical Biochemistry, 28, 49–54.
  • LEEMAN, T. D., TRANSON, C., BONNABRY, P. and DAYER, P., 1993, A major role for cytochrome P450TB (CYP2C subfamily) in the actions of non-steriodal anti-inflammatory drugs. Drugs in Experimental Clinical Research, 19, 189–195.
  • LELO, A., MINERS, J. 0., ROBSON, R. A. and BIRKETT, D. J., 1986, Quantitative assessment of caffeine partial clearances in man. British Journal of Clinical Pharmacology, 22, 183–186.
  • LIDE, D. R., 1990–91, Chemical Rubber Company Handbook of Chemistry and Physics (Boca Raton: CRC Press).
  • LOWN, K., KOLARS, J., TURGEON, D. K., MERION, R., WRIGHTON, S. A. and WATKINS, P. B., 1992, The erythromycin breath test selectively measures P450 IIIA in patients with severe liver disease. Clinical Pharmacology and Therapeutics, 51, 229–238.
  • LOWN, K. S., KOLARS, J. C., THUMMEL, K. E., BARNETT, J. L., KUNZE, K. L., WRIGHTON, S. A. and WATKINS, P. B., 1992, Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowl. Drug Metabolism and Disposition, 22, 947–955.
  • LOWN, K. S., THUMMEL, K. E., BENEDICT, P. E., SHEN, D. D., TURGEON, D. K., BERENT, S. and WATKINS, P. B. 1995, The erythromycin breath test predicts the clearance of midazolam. Clinical Pharmacology and Therapeutics, 57, 16–24.
  • LUCAS, D., BERTHOU, F., DREANO, Y., LOZACH, P., VOLANT, A. and MENEZ, J. F., 1993, Comparison of levels of cytochromes P450, CYP1A2, CYP2E1, and their related monooxygenase activities in human surgical liver samples. Alcohol in Clinical and Experimental Research, 17, 900–905.
  • MACKMAN, R., Guo, Z., GUENGERICH, F. P., ORTIZ DE MONTELLANO, P. R., 1996, Active site topology of human cytochrome P450 2E1. Chemical Research in Toxicology, 9, 223–226.
  • MAHGOUB, A., IDLE, J. R., DRING, L. G., LANCASTER, R. and SMITH, R. L., 1977, Polymorphic hydroxylation of debrisoquine in man. Lancet, ii, 584–586.
  • MANNERS, C. N., PAYLING, D. W. and SMITH, D. A., 1988, Distribution coefficient, a convenient term for the relation of predictable physico-chemical properties to metabolic processes. Xenobiotica, 18, 331–335.
  • MCGOURTY, J. C., SILAS, J. H., LENNARD, M. S., TUCKER, G. T. and WOODS, H. F., 1985, Metoprolol metabolism and debrisoquine oxidation polymorphism-population and family studies. British Journal of Clinical Pharmacology, 20, 555–566.
  • MuMANus, M. E., BURGESS, W. M., VERONESE, M. E., HUGGETT, A., QUATTROCHI, L. C. and TUKEY R. H., 1990, Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochrome P-450. Cancer Research, 50, 3367–3376.
  • MURRAY, M., 1984, Mechanisms of the inhibition of cytochrome P-450-mediated drug oxidation by therapeutic agents. Drug Metabolism Reviews, 18, 55–81.
  • NAKAMURA, J. and YAKATA, M., 1989, Assessing adrenocortical activity by determining levels of urinary free cortisol and urinary 6/3-hydroxycortisol. Acta Endocrinology, 120, 277–83.
  • NELSON E. and O'REILLY, I., 1961, Kinetics of carboxytolbutamide excretion following tolbutamide and carboxytolbutamide adminstration. Journal of Pharmacology and Experimental Therapeutics, 132, 103–109.
  • NOTARIANNI, L. J., OLIVER, S. E., DOBROCKY, P., BENNETT, B. N. and SILVERMAN, B. W., 1995, Caffeine as a metabolic probe: a comparison of the metabolic ratios used to assess CYP1A2 activity. British Journal of Clinical Pharmacology, 39, 65–69.
  • NSABIYUMVA, F., FURET, Y., AUTRER, E., JONVILLE, A. P. and BRETEAU, M., 1991, Oxidative polymorphism of detromethorphan in a Burundi population. European Journal of Clinical Pharmacology, 41, 75–77.
  • OLKKOLA, K. T., ARANKO, K., LUURILA, H., HILLER, A., SAARNIVAARA, L., HIMBERG, J. J. and NEUVONEN, P. J., 1993, A potentially hazardous interaction between erythromycin and midazolam. Clinical Pharmacology and Therapeutics, 53, 298–305.
  • O'SHEA, D., DAVIS, S. N., KIM, R. B. and WILKINSON, G. R., 1994, Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe for CYP2E1 activity. Clinical Pharmacology and Therapeutics, 56, 359–367.
  • PARK, B. K., 1982, Assessment of urinary 6/3-hydroxycortisol as an in vivo index of mixed function oxidase activity. British Journal of Clinical Pharmacology, 12, 97–102.
  • PARK, B. K. and KITTERINGHAM, N. R., 1989, Relevance and means of assessing induction and inhibition of drug metabolism in man. In G. G. Gibson (ed.), Progress in Drug Metabolism 11 (London: Taylor and Francis), pp. 1–59.
  • PARK, B. K. and KITTERINGHAM, N. R., 1990, Assessment of enzyme induction and enzyme inhibition in humans: toxicological implications. Xenobiotica, 20, 1171–1185.
  • PETER, R., BOCKER, R., BEAUNE, P. H., IWASAKI, M., GUENGERICH, F. P. and YANG, C. S., 1990, Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P450I1E1. Chemical Research and Toxicology, 3, 566–573.
  • PFANDL, B., MORIKE, K., WI, D., SCHARECK, W. and BREYER -PFAFF, U., 1992, Stereoselective inhibition of nortriptyline hydroxylation in man by quinidine. Xenobiotka, 22, 721–730.
  • PIRMOHAMED, M., WILLIAMS, D., MADDEN, S., TEMPLETON, E. and PARK, B. K., 1995, Metabolism and bioactivation of clozapine by human liver in vitro. Journal of Pharmacology and Experimental Therapeutics, 272, 984–990.
  • RENNER, E., WIETHOLTZ, H., HUGUENIN, P., ARNAUD, M. J. and PREISIG, R., 1984, Caffeine: a model compound for measuring liver function. Hepatology, 4, 38–46.
  • ROST, K. L. and ROOTS, I., 1994, Accelerated caffeine metabolism after omeprazole treatment as indicated by urinary metabolite ratios: coincidence with plasma clearance and breath test. Clinical Pharmacology and Therapeutics, 55, 402–411.
  • SARKAR, M. A. and JACKSON, B. J., 1994, Theophylline N-demethylations as probes for P4501A1 and P4501A2. Drug Metabolism and Disposition, 22, 827–833.
  • SAENGER, P., FORESTER, E. and KREAM, J., 1981,6fl-hydroxycortisol: a non-invasive indicator of enzyme induction. Journal of Clinical Endocrinology and Metabolism, 52, 381–384.
  • SCHMID, B., BIRCHER, J., PREISIG, R. and KUPFER, A., 1985, Polymorphic dextromethorphan metabolism: co-segregation of oxidative 0-demethylation with debrisoquin hydroxylation. Clinical Phar-macology and Therapeutics, 38, 618–624.
  • SESARDIC, D., BOOBIS, A. R., MURRAY, B. P., MURRAY, S., SEGURA, J., DE LA TORRE, R. and DAVIES,
  • D. S., 1990, Furafylline is a potent and selective inhibitor of cytochrome P4501A2 in man. British Journal of Clinical Pharmacology, 29, 651–663.
  • SHIMADA, T., YAMAZAKI, H., MIMURA, M., INUI, Y. and GUENGERICH, F. P., 1994, Interindividual variations in human cytochrome P-450 enzymes involved in the oxidations of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians. Journal of Pharmacology and Experimental Therapeutics, 270, 414–423.
  • SHOU, M., GROGAN, J. A., MANCEWICZ, J. A., KRAUSZ, K. W., GONZALEZ, F. J., GELBOIN, H. V. and KORZEKWA, K. R., 1994, Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry, 33, 6450–6455.
  • SIMOOYA O. O., NJUNN, E., HODJEGAN, A. R., LENNARD, M. S. and TUCKER, G. T., 1993, Debrisoquine and metoprolol oxidation in Zambians: a population study. Pharmacogenetics, 3, 205–208.
  • SINDRUP, S. H., BROSEN, K. and GRAM, L. F., 1992, Pharmacokinetics of the selective serotonin reuptake inhibitor paroxetine: nonlinearity and relation to the sparteine oxidation polymorphism. Clinical Pharmacology and Therapeutics, 51, 288–295.
  • SINDRUP, S. H., BROSEN, K., GRAM, L. F., HALLAS, J., SKJELBO, E., ALLEN, A., ALLEN, G. D., COOPER, S. M., MELLOWS, G., TASKER, C. G. and ZUSSMAN, B. D., 1992, The relationship between paroxetine and the sparteine oxidation polymorphism. Clinical Pharmacology and Therapeutics, 51, 278–287.
  • SKJELBO, E., BROSEN, K., HALLAS, J. and GRAM, L. F., 1991, The mephenytoin oxidation polymorphism is partially responsible for the N-demethylation of imipramine. Clinical Pharmacology and Therapeutics, 49, 18–23.
  • SKJELBO, E., GRAM, L. F. and BROSEN, K., 1993, The N-demethylation of imipramine correlates with the oxidation of (S)-mephenytoin (S1/2 ratio). A population study. British Journal of Clinical Pharmacology, 35, 331–334.
  • SLOAN, T. P., LANCASTER, R., SHAH, R. R., IDLE, J. R. and SMITH, R. L., 1983, Genetically determined oxidation capacity and the disposition of debrisoquine. British Journal of Clinical Pharmacology, 15, 443–450.
  • SMITH, D. A. and JONES, B. C., 1992, Speculations on the substrate structure-activity relationship (SSAR) of Cytochrome P450 enzymes. Biochemical Pharmacology, 44, 2089–2098.
  • SMITH, R. L., 1986, Introduction. Xenobiotica, 16, 361–365.
  • SOHN, D.-R., SHIN, S.-G., PARK, C.-W., KUSAKA, M., CHIBA, K. and ISHIZAKI, T., 1991, Metoprolol oxidation polymorphism in a Korean population: comparison with native Japanese and Chinese populations. British Journal of Clinical Pharmacology, 32, 504–507.
  • STROBL, G. R., VON KRUEDENER, S., SToCKIGT, J., GUENGERICH, F. P. and WOLFF, T., 1993, Development of a pharmacophore for inhibition of human liver cytochrome P450 2D6: molecular modelling and inhibition studies. Journal of Medicinal Chemistry, 36, 1136–1145.
  • SWINNEY, D. C., So, 0.-Y., WATSON, D. M., BERRY, P. W., WEBB, A. S., KERTESZ, D. J., SHELTON,
  • E. J., BURTON, P. M. and WALKER, K. A. M., 1994, Selective inhibition of mammalian lanosterol 14 a-demethylase by RS-21607 in vitro and in vivo. Biochemistry, 33, 4702–4713.
  • TASSANEEYAKUL W., BIRKETT, D. J., MEMANus, M. E., TASSANEEYAKUL W., VERONESE, M. E., ANDERSSON, T., TUKEY, R. H. and MINERS, J. 0., 1994, Caffeine metabolism by human hepatic cytochromes P450: contributions of 1A2, 2E1 and 3A isoforms. Biochemical Pharmacology, 47, 1767–1776.
  • TASSANEEYAKUL, W., VERONESE, M. E., BIRKETT, D. J., DOECKE, C. J., MCMANUS, M. E., SANSOM, L. N. and MINERS, J. 0., 1992, Co-regulation of phenytoin and tolbutamide metabolism in humans. British Journal of Clinical Pharmacology, 34, 494–498.
  • THOMAS, R. C. and 'REDA, G. J., 1966, The metabolic fate of tolbutamide in man and rat. Journal of Medicinal Chemistry, 9, 507–510.
  • THUMMEL, K. E., SHEN, D. D., PODOLL, T. D., KUNZE, K. L., TRAGER, W. F., HARTWELL, P. S., RAISYS V. A., MARSH, C. L., McVicAR, J. P., BARR, D. M., PERKINS, J. D. and CARITHERS Jr., R. L., 1994, Use of midazolam as a human cytochrome P450 3A probe: 1. In vitro—in vivo correlations in liver transplant patients. Journal of Pharmacology and Experimental Therapeutics, 271, 549–556.
  • THUMMEL, K. E., SHEN, D. D., PODOLL, T. MD., KUNZE, K. L., TRAGER, W. F., BACCHI, C. E., MARSH, C. L., McVicAR, J. P., BARR, D. M., PERKINS, J. D. and CARITHERS Jr., R. L., 1994, Use of midazolam as a human cytochrome P450 3A probe: II. Characterization of inter- and intraindividual hepatic CYP3A variability after liver transplantation. journal of Pharmacology and Experimental Therapeutics, 271, 557–566.
  • THUMMEL, K. E., SHEN, D. D., BACCHI, C. E., McVicAR, J. P., MARSH, C. L., PERKINS, J. D. and CARITHERS, R. L., 1992, Induction of human hepatic P4503A3/4 by phenytoin. Hepatology, 16, 160A (abstract).
  • THUMMEL, K. E., SHEN, D. D., CARITHERS, R. L., HARTWELL, P., PODOLL, T. D., TRAGER, W. F. and KUNZE, K. L., 1993, Prediction of in vivo midazolam clearance from hepatic CYP3A content and midazolam 1-hydroxylation activity in liver transplant patients. IS SX Proceedings, 4, 235–230.
  • TJIA, J. F., WEBBER, I. R. and BACK, D. J., 1991, Cyclosporin metabolism by the gastrointestinal mucosa. British Journal of Clinical Pharmacology, 31, 344–346.
  • TOUCHSTONE, J. L. and BLAKEMORE, W. S., 1961, Urinary 6/3-hydroxycortisol in adrenocortical hyperfunction. Journal of Clinical Endocrinology and Metabolism, 21, 263–270.
  • TURGEON, J., FISET, C., GIGUERE, R., GILBERT, M., MOERIKE, K., ROULEAU, J. R., KROEMER, H. K., EICHELBAU M., GRECH -BELANGER, 0. and BELANGER, P. M., 1991, Influence of debrisoquine phenotype and of quinidine on mexiletine disposition in man. Journal of Pharmacology and Experimental and Therapeutics, 259, 789–798.
  • TURGEON, D. K., LEICHTMAN, A. B. and BLAKE, D. S., 1994, Prediction of interpatient and intrapatient variation in OG 37325 dosing requirements by the erthromycin breath test. Transplantation, 57, 1736–1741.
  • TYBRING, G. and BERTILSSON, L., 1992, A methodological investigation on the estimation of the (S)-mephenytoin hydroxylation phenotype using the urinary SM ratio. Pharmacogenetks, 2, 241–243.
  • TYNDALE, R. F., SUNAHARA, R., INABA, T., KALOW, W., GONZALEZ, F. J. and NIZNIK, H. B., 1991, Neuronal cytochrome P450IID1 (debrisoquine/sparteine-type): potent inhibition of activity by ( —)-cocaine and nucleotide sequence identity to human hepatic P450 gene CYP2D6. Molecular Pharmacology, 40, 63–68.
  • VERONESE, M. E., MINERS, J. 0., RANDLES, D., GREGOV, D. and BIRKETT, D. J., 1990, Validation of the tolbutamide metabolic ratio for population screening with the use of sulfaphenazole to produce model phenotypic poor metabolizers. Clinical Pharmacology and Therapeutics, 47, 403–411.
  • VON -M OLTKE, L. L., GREENBLATT, D. J., DUAN, S. X., HARMATZ, J. S. and S HADER, R. I., 1994, In vitro prediction of the terfenadine-ketoconazole pharmacokinetic interaction. Journal of Clinical Pharmacology, 34, 1222–1227.
  • DE VRIES, J. D., SALPHATI, L., HORIE, S., BECKER, C. E. and HOENER, B.-A., 1994, Variability in the disposition of chlorzoxazone. Biopharmaceutics and Drug Disposition, 15, 587–597.
  • WADE, R. C., 1990, Solvation of the active site of cytochrome P450-cam. Journal of Computer-Aided Molecular, 4, 199–204.
  • WALKER, D. K., JONES, B. C. and SMITH, D. A., 1995, Differentiation of compounds which bind to P450 isozymes CYP2C9 and CYP3A4 by physicochemical properties. British Journal of Clinical Pharmacology, 40, 178P.
  • WANG, M.-H., WADE, D., CHEN, L., WHITE, S. and YANG, C. S. M., 1996, Probing the active site of rate and human cytochrome P450 2E1 with alcohols and carboxylic acids. Archives of Biochemistry and Biophysics, 317, 299–304.
  • WATKINS, P., 1994, Noninvasive tests of CYP3A enzymes. Pharmacogenetks, 4, 171–184.
  • WATKINS P. B., HAMILTON, T. A., ANNESLEY, T. M., ELLIS, C. N., KOLARS, J. C. and VORRHEES, J. J., 1990, The erythromycin breath test as a predictor of cyclosporin A blood levels. Clinical Pharmacology and Therapeutics, 48, 120–129.
  • WATKINS, P. B., MURRAY, S. A., WINKELMAN, L. G., HEUMAN, D. M., WRIGHTON, S. A. and GUZELIAN P. S., 1989, Erythromycin breath test as an assay of glucurocorticoid-inducible liver cytochromes P450. Journal of Clinical Investigation, 83, 688–697.
  • WEAVER, R. J., DICKINS, M. and BURKE, M. D., 1993, Cytochrome P450 2C9 is responsible for the hydroxylation of the naphthoquinone antimalarial 58C80 in human liver. Biochemical Phar-macology, 46, 1183–1197.
  • WEBER, I. R., PETERS, W. H. M. and BACK, D. J., 1992, Cyclosporin metabolism by human gas-trointestinal mucosal microsomes. British Journal of Clinical Pharmacology, 33, 661–664.
  • XIAODONG, S., GATTI, G., BARTOLI, A., CIPOLLA, G., CREMA, G. and PERUCCA, E., 1994, Omeprazole does not enhance the metabolism of phenacetin, a marker of CYP1A2 activity, in healthy volunteers. Therapeutic Drug Monitoring, 16, 248–250.
  • YAMAZAKI, H., Guo, Z. and GUENGERICH, F. P., 1995, Selectivity of cytochrome P4502E1 in chlorzoxazone 6-hydroxylation. Drug Metabolism and Disposition, 23, 438–440.
  • YUN, CH., OKERHOLM, R. A. and GUENGERICH, F. P., 1993, Oxidation of the antihistiminic drug terfenadine in human liver microsomes: role of cytochrome P450 3A(4) in the N-dealkylation and C-hydroxylation. Drug Metabolism and Disposition, 21, 403–409.
  • YUN, CH., WOOD, M., WOOD, A. J. J. and GUENGERICH, F. P., 1992, Identification of the pharmaco-genetic determinants of alfentanil metabolism: cytochrome P-4503A4. An explanation of the variable elimination clearance. Anaesthesiology, 77, 467–474.
  • ZUMOFF, B., BRADLOW, L., GALLAGHER, T. F. and HELLMAN, L., 1967, Cortisol metabolism in cirrhosis. Journal of Clinical Investigation, 46, 1735–1743.

Reprints and Corporate Permissions

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

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

Academic Permissions

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

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

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