Cytochrome P450 enzymes and drug metabolism - Basic concepts and methods of assessment

Cellular and Molecular Neurobiology

Volumn 19, Issue 3, 1999, Pages 309-323

  Glue, Paul ^a   Clement, Robert P ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Clinical assessment; Cytochrome P450; Drug interaction; Enzyme induction; Enzyme inhibition; In vitro assessment; Pharmacokinetics

Indexed keywords

BARBITURIC ACID DERIVATIVE; CAFFEINE; CIMETIDINE; CYTOCHROME P450; DEBRISOQUINE; DIAZEPAM; DISULFIRAM; DRUG; ENCAINIDE; FLUCONAZOLE; GESTAGEN; HEXOBARBITAL; IMIPRAMINE; KETOCONAZOLE; MEPHENYTOIN; NEUROLEPTIC AGENT; OMEPRAZOLE; PARACETAMOL; PHENYTOIN; PROPRANOLOL; PROTEIN; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIFAMPICIN; SEROTONIN UPTAKE INHIBITOR; SPARTEINE; THEOPHYLLINE; TOLBUTAMIDE; TRICYCLIC ANTIDEPRESSANT AGENT; UNINDEXED DRUG; WARFARIN;

ARTICLE; DIET; DRUG CONJUGATION; DRUG METABOLISM; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME INHIBITION; ENZYME SUBSTRATE; FRUIT JUICE; GENE SEQUENCE; GENETIC POLYMORPHISM; HUMAN; HYDROLYSIS; NONHUMAN; OXIDATION; PRIORITY JOURNAL; REDUCTION;

CYTOCHROME P-450 ENZYME SYSTEM; ENZYME ACTIVATION; HUMANS; PHARMACOKINETICS;

EID: 0032963648     PISSN: 02724340     EISSN: None     Source Type: Journal    
DOI: 10.1023/A:1006993631057     Document Type: Article

References (79)

1. Agundez, J. A. G., Ledesma, M. C., Ladero, J. M., and Benitez, J. (1995). Prevalence of CYP2D6 gene duplication and its repercussion on the oxidative phenotype in a white population. Clin. Pharmacol. Ther. 57:265-269.
2. Ahsan, C. H., Renwick, A. G., Waller, D. G., Challenor, V. F., George, C. F., and Amanulah, M. (1993). The influences of dose and ethnic origins on the pharmacokinetics of nifedipine. Clin. Pharmacol. Ther. 54:329-338.
3. Bailey, D. G., Arnold, J. M. O., and Spence, J. D. (1994). Grapefruit juice and drugs. Clin. Pharmacokinet. 26:91-98.
4. Balant-Gorgia, A. E., Balant, L. P., and Garrone, G. (1989). High blood concentrations of imipramine or clomipramine and therapeutic failure: a case report study using drug monitoring data. Ther. Drug Monit. 11:415-420.
5. Barry, M., and Feely, J. (1990). Enzyme induction and inhibition. Pharmacol. Ther. 48:71-94.
6. Benitez, J., Carrillo, J. A., and Herraiz, A. G. (1994). Higher incidence of side effects in psychiatric patients poor metabolizers of debrisoquine. Clin. Pharmacol. Ther. 55:170.
7. Bertilsson, L., Aberg-Wistedt, A., Gustafsson, L. L., and Nordin, C. (1985). Extremely rapid hydroxylation of debrisoquine: A case report with implication for treatment with nortriptyline and other tricyclic antidepressants. Ther. Drug. Monit. 7:478-480.
8. Bertilsson, L., Mellstrom, B., Sjoqvist, F., et al., (1981). Slow hydroxylation of nortriptyline and concomitant poor debrisoquine hydroxylation: Clinical implications. Lancet 1:560-561.
9. Bertilsson, L., Lou, L.-Q., Du, Y.-L., Liu, Y., Kuang, T.-Y., Liao, X.-M., Wang, K.-Y., Reviriego, J., Iselius, L., and Sjoqvist, F. (1992). Pronounced differences between native Chinese and Swedish populations in the polymorphic hydroxylations of debrisoquine and S-mephenytoin. Clin. Pharmacol. Ther., 51:388-397.
10. Bertilsson, L., Dahl, M.-L., Sjoqvist, F., Aberg-Wistedt, A., Humble, M., Johansson, I., Lundqvist, E., and Ingelman-Sundberg, M. (1993). Molecular basis for rational megaprescribing in ultrarapid hydroxylators of debrisoquine. Lancet 341:63.
11. Black, D. J., Kunze, K. L., Wienkers, L. C., Gidal, B. E., Seaton, T. L., McDonnell, N. D., Evans, J. S., Bauwens, J. E., and Trager, W. F. (1996). Warfarin-fluconazole II: A metabolically based drug interaction: in vivo studies. Drug Metab. Disp. 34:422-428.
12. Chen, S., King, V., Wedlund, P. J., and Hays, L. (1995). Cytochrome P450-2D6 (CYP2D6): Simplified screening for the A and B alleles and deficient enzyme expression. Clin. Pharmacol. Ther., 57:150.
13. Chen, S., Chou, W.-H., Blouin, R. A., Mao, Z., Humphries, L. L., Meek, C., Neill, J. R., Martin, W. L., Hays, L. R., and Wedlund, P. J. (1996). The cytochrome P450 2D6 (CYP2D6) enzyme polymorphism: Screening costs and influence on clinical outcomes in psychiatry. Clin. Pharmacol. Ther. 60:522-534.
14. Dahl, M.-L., Johannson, I., Palmertz, M. P., Ingelman-Sundberg, M., and Sjoqvist, F. (1992). Analysis of the CYP2D6 gene in relation to debrisoquine and desipramine hydroxylation in a Swedish population. Clin. Pharmacol. Ther. 51:12-17.
15. de Morais, S. M. F., Wilkinson, G. R., Blaisdell, J., Nakamura, K., Meyer, U. A., and Goldstein, J. A. (1994a). The major genetic defect responsible for the polymorphism of S-mephenytoin in human. J. Biol. Chem. 269:15419-15422.
16. de Morais, S. M. F., Wilkinson, G. R., Blaisdell, J., Meyer, U. A., Nakamura, K., and Goldstein, J. A. (1994b). Identification of a new genetic defect responsible for the polymorphism of S-mephenytoin metabolism in Japanese. Mol. Pharmacol. 46:594-598.
17. Doshi, B. S., Kulkarni, R. D., Chauhan, B. L., and Wilkinson, G. L. (1990). Frequency of impaired-mephenytoin hydroxylation in an Indian population. Br. J. Clin. Pharmacol. 30:779-780.
18. Eichelbaum, M. (1982). Defective oxidation of drugs: pharmacokinetic and therapeutic implications. Clin. Pharmacokinet. 7:1-22.
19. Engel, G., Hofmann, U., Heidemann, H., Cosme, J., and Eichelbaum, M. (1996). Antipyrine as a probe for human oxidative metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxyantipyrine, 3-hydroxmethylantipyrine, and norantipyrine formation. Clin. Pharmacol. Ther. 59:613-623.
20. Estabrook, R. W., (1996). The remarkable P450s: A historical overview of these versatile hemoprotein catalysts. FASEB J. 10:202-204.
21. Ford, J. M., Truman, C. A., Wilcock, G. K., and Roberts, C. J. (1993). Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer's disease. Clin. Pharmacol. Ther. 53:691-695.
22. Garfinkel, D. (1958). Studies on pig liver microsomes. 1. Enzymic and pigment composition of different microsomal fractions. Arch. Biochem. Biophys. 77:493-509.
23. Glue, P., and Banfield, C. R. (1996). Psychiatry, psychopharmacology and P450s. Human Psychopharmacol. 11:97-114.
24. Goff, D. C., Henderson, D. C., and Amico, E. (1992). Cigarette smoking in schizophrenia: relationship to psychopathology and medication side effects. Am. J. Psychiat. 149:1189-1194.
25. Gonzales, F. J., and Korzekwa, K. R. (1995). Cytochromes P450 expression systems. Annu. Rev. Pharmacol. Toxicol. 35:369-390.
26. Hammer, W., and Sjoqvist, F. (1967). Plasma levels of monomethylated tricyclic antidepressants during treatment with imipramine-like compounds. Life Sci. 6:1895-1903.
27. Harris, R. Z., Benet, L. Z., and Schwartz, J. B. (1995). Gender effects in pharmacokinetics and pharmaco-dynamics. Drugs 50: 222-239.
28. Harvey, A. T., and Preskorn, S. H. (1995). Interactions of serotonin reuptake inhibitors with tricyclic antidepressants. Arch. Gen. Psychiat. 52:783-784.
29. Heim, M., and Meyer, U. A. (1990). Genotyping of poor metabolizers of debrisoquine by allele-specific PCR amplification. Lancet 336:529-532.
30. Hong, J., Pan, J., Gonzalez, F. J., Gelboin, H. V., and Yang, C. S. (1987). The induction of a specific form of cytochrome P450 (P-450j) by fasting. Biochem. Biophys. Res. Commun. 142:1077-1083.
31. Honig, P. K., Wortham, D. C., Zamani, K., et al., (1993). Terfenadine-ketoconazole interaction. JAMA 269:1513-1518.
32. Hooper, W. D., and Qing, M.-S. (1990). The influence of age and gender on the stereoselective metabolism and pharmacokinetics of mephobarbital in humans. Clin. Pharmacol. Ther. 48:633-640.
33. Horsmans, Y., Desager, J. P., and Harvengt, C. (1992). Absence of CYP3A genetic polymorphism assessed by urinary excretion of 6-β hydroxyCortisol in 102 healthy subjects on rifampicin. Pharmacol. Toxicol. 71:258-261.
34. Hunt, C. M., Westerkam, W. R., and Stave, G. M. (1992). Effect of age and gender on the activity of human hepatic CYP3A. Biochem. Pharmacol. 44:275-283.
35. m2 in exon 4, in Japanese subjects. Clin. Pharmacol. Ther. 59:647-653.
36. Janicak, P. G., Javaid, J. I., Sharma, R. P., Comaty, J. E., Peterson, J., and Davis, J. M. (1989). Trifluoperazine plasma levels and clinical response. J. Clin. Psychopharmacol. 9:340-346.
37. Kappas, A., Anderson, K. E., Conney, A. H., and Alvares, A. P. (1976). Influence of dietary protein and carbohydrate on antipyrine and theophylline metabolism in man. Clin. Pharmacol. Ther. 20:643-653.
38. Kappas, A., Alvares, A. P., Anderson, K. E., Pantuck, E. J., Pantuck, C. B., Cahng, R., and Conney, A. H. (1978). Effect of charcoal-broiled beef on antipyrine and theophylline metabolism. Clin. Pharmacol. Ther. 23:445-450.
39. Koop, D. R. (1992). Oxidative and reductive metabolism by cytochrome P450 2E1. FASEB J. 2:724-730.
40. Krishna, D. R., and Klotz, U. (1994). Extrahepatic metabolism of drugs in humans. Clin. Pharmacokinet. 26:144-160.
41. Kroemer, H. K., and Eichelbaum, M. (1995). Molecular bases and clinical consequences of genetic cytochrome P450 2D6 polymorphism. Life Sci. 56:2285-2298.
42. Kunze, K. L., and Trager, W. F. (1996). Warfarin-fluconazole III: A rational approach to management of a metabolically based drug interaction. Drug Metab. Disp. 34:429-435.
43. Kunze, K. L., Wienkers, L. C., Thummel, K. E., and Trager, W. F. (1996). Warfarin-fluconazole I: Inhibition of the human cytochrome P450-dependent metabolism of warfain by fluconazole: In vitro studies. Drug Metab. Disp. 34:412-421.
44. Li, A. P., Kaminski, D. L., and Rasmussed, A. (1995). Substrates of human hepatic cytochrome P450 3A4. Toxicology 104:1-8.
45. May, D. G., Wilkinson, G. R., and Branch, R. A. (1994). Frequency distribution of dapsone N-hydroxlase, a putative probe for P4503A4 activity, in a white population. Clin. Pharmacol. Ther. 55:492-500.
46. Meyer, J. W., Woggon, B., Baumann, P., and Meyer, U. A. (1990). Clinical implications of slow sulphoxidation of thioridazine in a poor metabolizer of the debrisoquine type. Eur. J. Clin. Pharmacol. 39:613-614.
47. Murray, M. (1992). P450 enzymes: Inhibition mechanisms, genetic regulation and effects of liver disease. Clin. Pharmacokinet. 23:132-146.
48. Nafziger, N., and Bertino, J. S. (1989). Sex-related differences in theophylline pharmacokinetics. Eur. J. Clin. Pharmacol. 37:97-100.
49. Nakamura, K., Goto, F., Ray, W. A., McAllister, C. B., Jacqz, E., Wilkinson, G. R., and Branch, R. A. 1985. Interethnic differences in genetic polymorphism of debrisoquine and mephenytoin hydroxylation between Japanese and European populations. Clin. Pharmacol. Ther. 38:402-408.
50. Nebert, D. W., and Gonzales, F. J. (1987). P450 genes: Structure, evolution, and regulation. Annu. Rev. Biochem. 56:945-993.
51. Nebert, D. W., Nelson, D. R., Coon, M. J., Estabrook, R. W., Feyereisen, R., Fujii-Kuriyama, Gonzalez, F. J., Guengerich, F. P., Gunsalas, I. C., Johnson, E. F., Loper, J. C., Sato, R., Waterman, M. R., and Waxman, D. J. (1991). The P450 superfamily; Update on new sequences, gene mapping, and recommended nomenclature. DNA Cell Biol. 10:1-14.
52. Nelson, D. R., Kamataki, T., Waxman, D. J., Guengerich, F. P., Estabrook, R. W., Feyerelsen, R., Gonzalez, F. J., Coon, M. J., Gunsalus, I. C., Gotoh, A., Okuda, K., and Nebert, D. W. (1993). The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol. 12:1-51.
53. Nielsen, F., Roshohn, J.-U., and Brosen, K. (1995). Lack of relationship between quinidine pharmacokinetics and the spartein oxidation polymorphism. Eur. J. Clin. Pharmacol. 48:501-504.
54. Omura, T., and Sato, R. (1962). A new cytochrome in liver microsomes. J. Biol. Chem. 237:PC1375-PC1376.
55. Parkinson, A. (1996). An overview of current cytochrome P450 technology for assessing the safety and efficacy of new materials. Toxicol. Pathol. 24:45-57.
56. Perrot, N., Nalpas, B., Yang, C. S., and Beaune, P. H. (1989). Modulation of cytochrome P450 isozymes in human liver, by ethanol and drug intake. Eur. J. Clin. Pharmacol. 19:549-555.
57. Popli, A., Baldessarini, R. J., and Cole, J. O. (1995). Interactions of serotonin reptake inhibitors with tricyclic antidepressants - in reply. Arch. Gen. Psychiat. 52:784-785.
58. Potkin, S. G., She, Y., Pardes, H., Phelps, B. H., Zhou, D., Shu, L., Korpi, E., and Wyatt, R. J. (1984) Haloperidol concentrations elevated in Chinese patients. Psychiatry Res. 12:167-172.
59. Ratanasavanh, D., Beaune, P., Morel, F. et al. (1991). Intralobular distribution and quantitation of cytochrome P450 enzymes in human liver as a function of age. Hepatology 13:1142-1151.
60. Relling, M. V., Lin, J.-S., Ayers, G. D., and Evans, W. E. (1992). Racial and gender differences in N-acetyltransferase, xanthine oxidase, and CYP1A2 activities. Clin. Pharmacol. Ther. 52:643-658.
61. Rodrigues, A. D. (1994). Use of in vitro human metabolism studies in drug development. Biochem. Pharmacol. 48:2147-2156.
62. Rowland, M. (1975). Kinetics of drug-drug interactions. In Teorell, T., Dedrick, R. L., and Candliffe, P. G. (eds.), Pharmacology and Pharmacokinetics, Plenum Press, London, pp. 321-386.
63. Rudorfer, M. V., Lane, E. A., Chang, W.-H., et al. (1984). Desipramine pharmacokinetics in Chinese and Caucasian volunteers. Br. J. Clin. Pharmacol. 17:433-440.
64. Schuetz, J. D., Beach D. L., and Guzelian, P. S. (1994). Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. Pharmacogenetics, 4:11-20.
65. Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., Guengerich, F. P. (1994). Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals; studies with liver microsomes of 30 Japanese and 30 Caucausians. J. Pharmacol. Exp. Ther. 270:414-423.
66. Spatzenegger, M., and Jaeger, W. (1995). Clinical importance of hepatic cytochrome P450 in drug metabolism. Drug Metab. Rev. 27:397-417.
67. Spina, E., Ancione, M., Di Rosa, A. E., et al. (1992). Polymorphic debrisoquine oxidation and acute neuroleptic-induced adverse effects. Eur. J. Clin. Pharmacol. 42:347-348.
68. Spina, E., Avenoso, A., Campo, G., Caputi, A. P., and Perucca, E. (1995). The effect of carbamazepine on the 2-hydroxylation of desipramine. Psychopharmacology 117:413-416.
69. Vinarova, E., Vinar, O., and Kalvach, Z. (1984). Smokers need higher doses of neuroleptic drugs. Biol. Psychiat. 19:1265-1268.
70. von Moltke, L. L., Greenblatt, D. J., Cotreau-Bibbo, M. M., Duan, S. X., Harmatz, J. S., and Shader, R. I. (1994a). Inhibition of desipramine hydroxylation in vitro by serotonin reuptake inhibitor antidepressants, and by quinidine and ketoconazole: A model system to predict drug interactions in vivo. J. Pharmacol. Exp. Ther. 268:1278-1283.
71. von Moltke, L. L., Greenblatt, D. J., Cotreau-Bibbo, M. M., Harmatz, J. S., and Shader, R. I. (1994b). Inhibitors of alprazolam metabolism by serotonin reuptake inhibitor antidepressants, ketoconazole and quinidine. Br. J. Clin. Pharmacol. 38:23-31.
72. von Moltke, L. L., Greenblatt, D. J., Harmatz, L. S., and Shader, R. I. (1994c). Cytochromes in psychopharmacology. J. Clin. Psychopharmacol. 14:1-4.
73. von Moltke, L. L., Greenblatt, D. J., Court, M. H., Duan, S. X., Harmatz, J. S., and Shader, R. I. (1995). Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: Comparison with other selective serotonin reuptake inhibitor antidepressants. J. Clin. Psychopharmacol. 15:125-131.
74. Walle, T., Walle, U. K., Cowart, T. D. et al. (1989). Pathway-selective sex differences in the metabolic clearance of propranolol. Clin. Pharmacol. Ther. 46:257-263.
75. Waterman, M. R., Jenkins, C. M., and Pikuleva, I. (1995). Gentically engineered bacterial cells and applications. Toxicol. Lett, 82/83:807-813.
76. 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 glucocorticoid-inducible liver cytochromes P-450. J. Clin. Invest. 83:688-697.
77. Wrighton, S. A., and Stevens, J. C. (1992). The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. Toxicol. 22:1-21.
78. Yang, C. S., Brady, J. F., and Hong, J.-Y. (1992). Dietary effects on cytochromes P450, xenobiotic metabolism, and toxicity. FASEB J. 6:737-744.
79. Yue, O. Y., Svensson, J.-O, Alm, C., Sjoqvist, F., and Sawe, J. (1989). Interindividual and interethnic differences in the demethylation and glucuronidation of codeine. Br. J. Clin. Pharmacol. 28:629-637.