Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction

Advanced Drug Delivery Reviews

Volumn 27, Issue 2-3, 1997, Pages 99-127

  Thummel, Kenneth E ^a   Kunze, Kent L ^a   Shen, Danny D ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

Bioavailability; Cytochrome P450 3A (CYP3A); First pass metabolism; Pharmacokinetics

Indexed keywords

CATALYSIS; DRUG INTERACTIONS; DRUG THERAPY; ENZYMES; EXTRACTION; MATHEMATICAL MODELS; METABOLISM; OXIDATION; SUBSTRATES;

CYTOCHROMES P450 3A; FIRST PASS METABOLISM; ORAL BIOAVAILABILITY;

PHARMACOKINETICS;

AMIODARONE; AMITRIPTYLINE; BROMOCRIPTINE; CHLORPROMAZINE; CODEINE; CYCLOSPORIN; CYTOCHROME P450; CYTOCHROME P450 ISOENZYME; DESIPRAMINE; DICLOFENAC; DILTIAZEM; ERYTHROMYCIN; FELODIPINE; ISOPRENALINE; LABETALOL; LIDOCAINE; LOSARTAN; MEVINOLIN; MIDAZOLAM; MORPHINE; NEFAZODONE; NICARDIPINE; NIFEDIPINE; OMEPRAZOLE; PROPRANOLOL; SAQUINAVIR; TERBUTALINE; TERFENADINE; UNINDEXED DRUG; VERAPAMIL;

BIOAVAILABILITY; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG ELIMINATION; DRUG METABOLISM; ENZYME SPECIFICITY; FIRST PASS EFFECT; HUMAN; INTESTINE ABSORPTION; PRIORITY JOURNAL; REVIEW;

EID: 0342437515     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0169-409X(97)00039-2     Document Type: Review

References (215)

1. Artursson P. Epithelial transport of drugs in cell culture. I: A model for studying the passive diffusion of drugs over intestinal absorptive (Caco-2) cells. J. Pharm. Sci. 79:1990;476-482.
2. Artursson P., Karlsson J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Comm. 175:1991;880-885.
3. Meunier V., Bourrie M., Berger Y., Fabre G. The human intestinal epithelial cell line Caco-2; pharmacological and pharmacokinetic applications. Cell Biol. Toxicol. 11:1995;187-194.
4. 1 and Caco-2 cell lines as models for studying intestinal paracellular drug absorption. Pharm. Res. 13:1996;216-221.
5. J. Caldwell, S.C. Mitchell, Metabolic pathways, in: C. Hansch, P.G. Sammes, J.B. Taylor (Eds.), Comprehensive Medicinal Chemistry. The Rational Design, Mechanistic Study & Therapeutic Application of Chemical Compounds, vol. 5. Pergamon Press, Oxford, 1990, pp. 143-162.
6. Iwatsubo T., Hirota N., Ooie T., Suzuki H., Shimada N., Chiba K., Ishizaki T., Green C.E., Tyson C.A., Sugiyama Y. Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data. Pharmacol. Ther. 73:1997;147-171.
7. Wrighton S.A., Stevens J.C. The human hepatic cytochromes P450 involved in drug metabolism. Crit. Rev. Toxicol. 22:1992;1-21.
8. F.P. Guengerich, Human cytochrome P450 enzymes, in: Paul R. Ortiz de Montellano (Ed.), Cytochrome P450: Structure, Mechanism, and Biochemistry, Second Edition, Plenum Press, New York, 1995, pp. 473-535.
9. Shimada T., Yamazaki H., Mimura M., Inui Y., Guengerich F.P. 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 Caucasians. J. Pharmacol. Exp. Ther. 270:1994;414-423.
10. Gorski J.C., Hall S.D., Jones D.R., VandenBranden M., Wrighton S.A. Regio-selective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem. Pharmacol. 47:1994;1643-1653.
11. Rowland M., Benet L.Z., Graham G.G. Clearance concepts in pharmacokinetics. J. Pharmacokinet. Biopharm. 1:1973;123-137.
12. Wilkinson G.R., Shand D.G. A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18:1975;377-390.
13. Pang K.S., Rowland M. Hepatic clearance of drugs. I. Theoretical considerations of a 'well-stirred model' and a 'parallel tube' model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J. Pharmacokinet. Biopharm. 5:1977;625-651.
14. Bass L., Robinson P., Bracken A.J. Hepatic elimination of flowing substrates: the distributed model. J. Theor. Biol. 72:1978;161-184.
15. Roberts M.S., Rowland M. A dispersion model of hepatic elimination. J. Pharmacokinet. Biopharm. 14:1986;227-308.
16. Gillette J.R. Overview of drug-protein binding. Ann. New York Acad. Sci. 226:1973;6-17.
17. Wilkinson G.R. Clearance approaches in pharmacology. Pharmacol. Rev. 39:1987;1-47.
18. Edwards D.J. Evidence favoring the venous equilibrium model for hepatic clearance of (S)-(-)-propranolol. J. Pharm. Sci. 73:1984;1498-1499.
19. Iwatsubo T., Hirota N., Ooie T., Suzuki H., Sugiyama Y. Prediction of in vivo drug disposition from in vitro data based on physiological pharmacokinetics. Biopharm. Drug Disp. 17:1996;273-310.
20. Houston J.B. Utility of in vitro drug metabolism data in predicting in vivo metabolic clearance. Biochem. Pharmacol. 47:1994;1469-1479.
21. K.S. Pang, M. Chiba, Metabolism: scaling-up from in vitro to organ and whole body, in: Peter J. Welling, Luc P. Balaut (Eds.), Handbook of Experimental Pharmacology, vol. 110. Springer, 1994, pp. 101-187.
22. Yamazaki H., Ueng Y.-F., Shimada T., Guengerich F.P. Roles of divalent metal ions in oxidations catalyzed by recombinant cytochrome P450 3A4 and replacement of NADPH-cytochrome P450 reductase with other flavoproteins, ferredoxin, and oxygen surrogates. Biochem. 34:1995;8380-8389.
23. Maenpaa J.V.A., Hall S.D., Ring B.J., Strom S.C., Wrighton S.A. The effect of different assay conditions on the stimulation in vitro of midazolam metabolism by CYP3A4 and CYP3A7. ISSX Proc. 10:1996;249.
24. Imaoka S., Imai Y., Shimada T., Funae Y. Role of phospholipids in reconstituted cytochrome P450 3A form and mechanism of their activation of catalytic activity. Biochemistry. 31:1992;6063-6069.
25. Rane A., Wilkinson G.R., Shand D.G. Prediction of hepatic extraction ratio from in vitro measurement of intrinsic clearance. J. Pharmacol. Exp. Ther. 200:1977;420-424.
26. Baarnhielm C., Dahlback H., Skanberg I. In vivo pharmacokinetics of felodipine predicted from in vitro studies in rat, dog and man. Acta Pharmacol. Toxicol. 59:1986;113-122.
27. Bayliss M.K., Bell J.A., Jenner W.N., Wilson K. Prediction of intrinsic clearance of loxtidine from kinetic studies in rat, dog and human hepatocytes. Biochem. Soc. Trans. 18:1990;1198-1199.
28. 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., Carithers R.L. Jr. Use of midazolam as human cytochrome P450 3A probe: I. In vitro-in vivo correlations in liver transplant patients. J. Pharmacol. Exp. Ther. 271:1994;549-556.
29. Thummel K.E., O'Shea D., Paine M.F., Shen D.D., Kunze K.L., Perkins J.D., Wilkinson G.R. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin. Pharmacol. Ther. 59:1996;491-502.
30. Kroemer H.K., Echizen H., Heidemann H., Eichelbaum M. Predictability of the in vivo metabolism of verapamil from in vitro data: contribution of individual metabolic pathways and stereoselective aspects. J. Pharmacol. Exp. Ther. 260:1992;1052-1057.
31. Hoener B.-A. Predicting the hepatic clearance of xenobiotics in humans from in vitro data. Biopharm. Drug Disp. 15:1994;295-304.
32. Rettie A.E., Eddy A.C., Heimark L.D., Gibaldi M., Trager W.F. Characteristics of warfarin hydroxylation catalyzed by human liver microsomes. Drug Metab. Dispos. 17:1989;265-270.
33. Wilkinson G.R. Plasma and tissue binding considerations in drug disposition. Drug Metab. Rev. 14:1983;427-465.
34. Edwards R.J., Murray B.P., Singleton A.M., Boobis A.R. Orientation of cytochromes P450 in the endoplasmic reticulum. Biochemistry. 30:1991;71-76.
35. Shand D.G., Hammil S.C., Aaonsen L., Pritchett E.L.C. Reduced verapamil clearance during long-term oral administration. Clin. Pharmacol. Ther. 30:1981;701-703.
36. Siddoway L.A., Thompson K.A., McAllister C.B., Wang T., Wilkinson G.R., Roden D.M., Woosley R.L. Polymorphism of propafenone metabolism and disposition in man: clinical and pharmacokinetic consequences. Circulation. 75:1987;785-791.
37. Silber B.M., Holford N.H.G., Riegelman S. Dose-dependent elimination of propranolol and its major metabolites in humans. J. Pharm. Sci. 72:1983;725-732.
38. Shepherd A.M.M., Irvine N.A., Ludden T.M., Lin M.-S., McNay J.L. Effect of oral dose size on hydralazine kinetics and vasodepressor response. Clin. Pharmacocol. Ther. 36:1984;595-600.
39. Sindrup S.H., Brosen K., Gram L.F. Nonlinear kinetics of imipramine in low and medium plasma level ranges. Ther. Drug Monit. 12:1990;445-449.
40. Sindrup S.H., Brosen K., Gram L.F. Pharmacokinetics of the selective serotonin reuptake inhibitor paroxetine: nonlinearity and relation to the sparteine oxidation polymorphism. Clin. Pharmacol. Ther. 51:1992;288-295.
41. Axelson J.E., Chan G.L.Y., Kirsten E.B., Mason W.D., Lanman R.C., Kerr C.R. Food increases the bioavailability of propafenone. Br. J. Clin. Pharmacol. 23:1987;735-741.
42. Melander A., Danielson K., Hanson A., Rudell B., Schersten B., Thulin T., Wahlin E. Enhancement of hydralazine bioavailability by food. Clin. Pharmacol. Ther. 22:1977;104-107.
43. Shepherd A.M., Irvine N.A., Ludden T.M. Effect of food on blood hydralazine levels and response in hypertension. Clin. Pharmacol. Ther. 36:1984;14-17.
44. Melander A., Danielson K., Schersten B., Wahlin E. Enhancement of the bioavailability of propranolol and metoprolol by food. Clin. Pharmacol. Ther. 22:1977;108-112.
45. Rubin G.M., Tozer T.N. Hepatic binding and Michaelis-Menten metabolism of drugs. J. Pharm. Sci. 75:1986;660-663.
46. Wrighton S.A., Stevens J.C., Becker G.W., VandenBranden M. Isolation and characterization of human liver cytochrome P450 2C19: correlation between 2C19 and S-mephenytoin 4′-hydroxylation. Arch. Biochem. Biophys. 306:1993;240-245.
47. Haining R.L., Hunter A.P., Veronese M.E., Trager W.F., Rettie A.E. Allelic variants of human cytochrome P450 2C9: baculovirus-mediated expression, purification, structural characterization, substrate stereoselectivity, and prochiral selectivity of the wild-type and I359L mutant forms. Arch. Biochem. Biophys. 333:1996;447-458.
48. Rettie A.E., Wienkers L.C., Gonzalez F.J., Trager W.F., Korzekwa K.R. Impaired (S)-warfarin metabolism catalysed by the R144C allelic variant of CYP2C9. Pharmacogenetics. 4:1994;39-42.
49. Hall S.D., Hamman M.A., Rettie A.E., Wienkers L.C., Trager W.F., VandenBranden M., Wrighton S.A. Relationships between the levels of cytochrome P4502C9 and its prototypic catalytic activities in human liver microsomes. Drug Metab. Dispos. 22:1994;975-978.
50. Bertilsson L. Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19. Clin. Pharmacokinet. 29:1995;192-209.
51. Daly A.K. Molecular basis of polymorphic drug metabolism. J. Mol. Med. 73:1995;539-553.
52. Lennard M.S., Tucker G.T., Silas J.H., Freestone S., Ramsay L.E., Woods H.F. Differential stereoselective metabolism of metoprolol in extensive and poor debrisoquin metabolizers. Clin. Pharmacol. Ther. 34:1983;732-737.
53. Silas J.H., Lennard M.S., Tucker G.T., Ramsay L.E., Woods H.F. Polymorphic metabolism of β-adrenoceptor antagonists. Br. J. Clin. Pharmac. 17:1984;11S-19S.
54. Johnson J.A., Burlew B.S. Metoprolol metabolism via cytochrome P4502D6 in ethnic populations. Drug Metab. Dispos. 24:1996;350-355.
55. Sindrup S.H., Soren H.S., Bronsen K., Gram L.F., Hallas J., Skjelbo E., Allen A., Allen G.D., Cooper S.M., Mellows G., Tasker T.C.G., Zussman B.D. The relationship between paroxetine and sparteine oxidation polymorphism. Clin. Pharmacol. Ther. 51:1992;278-287.
56. Linnet K., Wiborg O. Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. Clin. Pharmacol. Ther. 60:1996;41-47.
57. Watkins P.B., Wrighton S.A., Maurel P., Schuetz E.G., Mendez-Picon G., Parker G.A., Guzelian P.S. Identification of an inducible form of cytochrome P-450 in human liver. Proc. Natl. Acad. Sci. USA. 83:1985;6310-6314.
58. Shaw P.M., Barnes T.S., Cameron D., Engeset J., Melvin W.T., Omar G., Petrie J.C., Rush W.R., Snyder C.P., Whiting P.H., Wolf C.R., Burke M.D. Purification and characterization of an anticonvulsant-induced human cytochrome P-450 catalysing cyclosporin metabolism. Biochem. J. 263:1989;653-663.
59. Thummel K.E., Shen D.D., Podoll T., Kunze K.L., Trager W.F., Bacchi C.E., Marsh C.L., McVicar J.P., Barr D.M., Perkins J.D., Carithers Jr R.L. Use of midazolam as a human cytochrome P450 3A probe: II. Characterization of inter- and intra-individual hepatic P450 3A variability after liver transplantation. J. Pharmacol. Exp. Ther. 271:1994;557-566.
60. Schuetz E.G., Schuetz J.D., Strom S.C., Thompson M.T., Fisher R.A., Molowa D.T., Li D., Guzelian P.S. Regulation of human liver cytochromes P-450 in family 3A in primary and continuous culture of human hepatocytes. Hepatology. 18:1993;1254-1262.
61. Combalbert J., Fabre I., Fabre G., Dalet I., Derancourt J., Cano J.P., Maurel P. Metabolism of cyclosporin A. IV. Purification and identification of the rifampin-inducible human liver cytochrome P-450 (Cyclosporin A Oxidase) as a product of P450IIIA gene subfamily. Drug Metab. Dispos. 17:1989;197-207.
62. Kolars J.C., Schmiedlin-Ren P., Schuetz J.D., Fang C., Watkins P.B. Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J. Clin. Invest. 90:1992;1871-1878.
63. Zhou H.H., Anthony L.B., Wood A.J.J., Wilkinson G.R. Induction of polymorphic 4′-hydroxylation of S-mephenytoin by rifampicin. Br. J. Clin. Pharmacol. 30:1990;471-475.
64. Diaz D., Fabre I., Daujat M., Saint Aubert B., Bories P., Michel H., Maurel P. Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. Gastroenterology. 99:1990;737-747.
65. 13C-[N-3-methyl]-caffeine breath test in poor and extensive metabolizers of S-mephenytoin. Clin. Pharmacol. Ther. 52:1992;170-180.
66. Sherson D., Sigsgaard T., Overgaard E., Loft S., Poulsen H.E., Jongeneelen F.J. Interaction of smoking, uptake of polycyclic aromatic hydrocarbons, and cytochrome P450IA2 activity among foundry workers. Br. J. Industr. Med. 49:1992;197-202.
67. Hellriegel E.T., Bjornsson T.D., Hauck W.W. Interpatient variability in bioavailability is related to the extent of absorption: implications for bioavailability and bioequivalence studies. Clin. Pharmacol. Ther. 60:1996;601-607.
68. Watkins P.B., Wrighton S.A., Schuetz E.G., Molowa D.T., Guzelian P.S. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J. Clin. Invest. 80:1987;1029-1036.
69. DeWaziers I., Cugnenc P.H., Yang C.S., Leroux J.-P., Beaune P.H. Cytochrome P450 isozymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues. J. Pharmacol. Exper. Ther. 253:1990;387-394.
70. McKay J.A., Murray G.I., Weaver R.J., Ewen S.W.B., Melvin W.T., Burke M.D. Xenobiotic metabolising enzyme expression in colonic neoplasia. Gut. 34:1993;1234-1239.
71. Lown K.S., Kolars J.C., Thummel K.E., Barnett J.L., Kunze K.L., Wrighton S.A., Watkins P.B. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test. Drug Metab. Dispos. 22:1994;947-955.
72. McKinnon R.A., Burgess W.M., Hall P., de la M., Roberts-Thompson S.J., Gonzalez F.J., McManus M.E. Characterization of CYP3A gene subfamily expression in human gastrointestinal tissues. Gut. 36:1995;259-267.
73. Kivisto K.T., Bookjans G., Fromm M.F., Griese E.-U., Munzel P., Kroemer H.K. Expression of CYP3A4, CYP3A5 and CYP3A7 in human duodenal tissue. Br. J. Clin. Pharmacol. 42:1996;387-389.
74. Pacifici G.M., Bencini C., Rane A. Presystemic glucuronidation of morphine in humans and rhesus monkeys: subcellular distribution of the UDP-glucuronyltransferase in the liver and intestine. Xenobiotica. 16:1986;123-128.
75. Rogers S.M., Back D.J., Orme M.L'E. Intestinal metabolism of ethinyloestradiol and paracetamol in vitro: studies using Ussing chambers. Br. J. Clin. Pharmacol. 23:1987;727-734.
76. Peters W.H.M., Kock L., Nagengast F.M. F., Kremers P.G. Biotransformation enzymes in human intestine: critical low levels in the colon. Gut. 32:1991;408-412.
77. Cappiello M., Giuliani L., Pacifici G.M. Distribution of UDP-glucuronosyltransferase and its endogenous substrate uridine 5'-diphosphoglucuronic acid in human tissues. Eur. J. Clin. Pharmacol. 41:1991;345-350.
78. Prueksaritanont T., Gorham L.M., Hochman J.H., Tran L.O., Vyas K.P. Comparative studies of drug-metabolizing enzymes in dog, monkey, and human small intestines, and in Caco-2 cells. Drug Metab. Dispos. 24:1996;634-642.
79. Raoof A.A., van Obbergh L.J., de Ville de Goyet J., Verbeeck R.K. Extrahepatic glucuronidation of propofol in man: possible contribution of gut wall and kidney. Eur. J. Clin. Pharmacol. 50:1996;91-96.
80. Pacifici G.M., Eligi M., Giuliani L. (+) and (-) terbutaline are sulphated at a higher rate in human intestine than in liver. Eur. J. Clin. Pharmacol. 45:1993;483-487.
81. Pesola G.R., Walle T. Stereoselective sulfate conjugation of isoproterenol in humans: comparison of hepatic, intestinal, and platelet activity. Chirality. 5:1993;602-609.
82. Her C., Szumlanski C., Aksoy I.A., Weinshilbaum R.M. Human jejunal estrogen sulfotransferase and dehydroepiandrosterone sulfotransferase. Immunochemical characterization of interindividual variation. Drug Metab. Dispos. 24:1996;1328-1335.
83. Pacifici G.M., Franchi M., Bencini C., Repetti F., Di Lascio N., Muraro G.B. Tissue distribution of drug-metabolizing enzymes in humans. Xenobiotica. 18:1988;849-856.
84. Engeland K., Maret W. Extrahepatic, differential expression of four classes of human alcohol dehydrogenase. Biochem. Biophys. Res. Comm. 193:1993;47-53.
85. Farres J., Moreno A., Crosas B., Peralba J.M., Allali-Hassani A., Hjelmqvist L., Jornvall H., Pares X. Alcohol dehydrogenase of class IV (66-ADH) from human stomach cDNA sequence and structure/function relationships. Eur. J. Biochem. 224:1994;549-557.
86. Haber P.S., Gentry R.T., Mak K.M., Mirmiran-Yazdy S.A.A., Greenstein R.J., Lieber C.S. Metabolism of alcohol by human gastric cells: relation to first-pass metabolism. Gastroenterology. 111:1996;863-870.
87. Kolars J.C., Lown K.S., Schmeidlin-Ren P., Ghosh M., Fang C., Wrighton S.A., Merion R.M., Watkins P.B. CYP3A gene expression in human gut epithelium. Pharmacogenetics. 4:1994;247-259.
88. M.F. Paine, M. Khalighi, J.M. Fisher, D.D. Shen, K.L. Kunze, C.L. Marsh, J.D. Perkins, K.E. Thummel, Characterization of inter- and intra-intestinal differences in human CYP3A-dependent metabolism, (1997) submitted.
89. Wrighton S.A., Brian W.R., Sari M.-A., Iwasaki M., Guengerich F.P., Raucy J.L., Molowa D.T., VandenBranden M. Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol. Pharamcol. 38:1990;207-213.
90. Jounaidi Y., Hyrailles V., Gervot L., Maurel P. Detection of a CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein. Biochem. Biophys. Res. Comm. 221:1996;466-470.
91. 3. Mol. Pharmacol. 51:1997;741-754.
92. Gan L.-S.L., Moseley M.A., Khosla B., Augustijns P.F., Bradshaw T.P., Hendren R.W., Thakker D.R. CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells. Interaction between the two biochemical barriers to intestinal transport. Drug Metab. Dispos. 24:1996;344-349.
93. Lang C.C., Brown R.M., Kinirons M.T., Deathridge M.-A., Guengerich F.P., Kelleher D., O'Briain D.S., Ghishan F.K., Wood A.J.J. Decreased intestinal CYP3A in celiac disease: reversal after successful gluten-free diet: a potential source of interindividual variability in first-pass drug metabolism. Clin. Pharmacol. Ther. 59:1996;41-46.
94. Fromm M.F., Busse D., Kroemer H.K., Eichelbaum M. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology. 24:1996;796-801.
95. Hebert M.F., Roberts J.P., Prueksaritanont T., Benet L.Z. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin. Pharmacol. Ther. 52:1992;453-457.
96. Freeman D.J., Laupacis A., Keown P.A., Stiller C.R., Carruthers S.G. Evaluation of cyclosporin-phenytoin interaction with observations on cyclosporin metabolites. Br. J. Clin. Pharmacol. 18:1984;887-893.
97. Wu C.-Y., Benet L.Z., Hebert M.F., Gupta S.K., Rowland M., Gomez D.Y., Wacher V.J. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin. Pharmacol. Ther. 58:1995;492-497.
98. Mahon W.A., Inaba T., Stone R.M. Metabolism of flurazepam by the small intestine. Clin. Pharmacol. Ther. 22:1977;228-233.
99. Vickers A.E.M., Fischer V., Connors S., Fisher R.L., Baldeck J.-P., Maurer G., Brendel K. Cyclosporin A metabolism in human liver, kidney, and intestine slices. Comparison to rat and dog slices and human cell lines. Drug Metab. Dispos. 20:1992;802-809.
100. Tjia J.F., Webber I.R., Back D.J. Cyclosporin metabolism by the gastrointestinal mucosa. Br. J. Clin. Pharmac. 31:1991;344-346.
101. Vickers A.E.M., Fisher R.L., Brendel K., Guertler J., Danncker R., Keller B., Fischer V. Sites of biotransformation for the cyclsporin derivative SDZ IMM 125 using human liver and kidney slices and intestine. Drug Metab. Dispos. 23:1995;327-333.
102. Lampen A., Christians U., Guengerich F.P., Watkins P.B., Kolars J.C., Bader A., Gonschior A.-K., Dralle H., Hackbarth I., Sewing K.-F. Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability. Drug Metab. Dispos. 23:1995;1315-1324.
103. Fitzsimmons M.E., Collins J.M. Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytcochrome P4503A4. Drug Metab. Dispos. 25:1997;256-266.
104. Flinois J.-P., Chabin M., Dufour A., DeWaziers I., Mas-Chamberlin C., Beaune P.H. Metabolism rate of oxodipine in rats and humans: comparison of in vivo and in vitro data. J. Pharmacol. Exp. Ther. 261:1992;381-386.
105. Wilkinson P.K. Pharmacokinetics of ethanol: a review. Alcohol. Clin. Exp. Res. 4:1980;6-21.
106. Levitt M.D., Levitt D.G. The critical role of the rate of ethanol absorption in the interpretation of studies purporting to demonstrate gastric metabolism of ethanol. J. Pharmacol. Exper. Ther. 269:1994;297-304.
107. Pestalozzi D.M., Buhler R., von Wartburg J.P., Hess M. Immunohistochemical localization of alcohol dehydrogenase in the human gastrointestinal tract. Gastroenterology. 85:1983;1011-1016.
108. Frezza M., Di Padova C., Pozzato G., Terpin M., Baraona E., Lieber C.S. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. New Engl. J. Med. 322:1990;95-99.
109. Baraona E., Gentry R.T., Lieber C.S. Bioavailability of alcohol: role of gastric metabolism and its interaction with other drugs. Dig. Dis. Sci. 12:1994;351-367.
110. 3 phenotype and gastric region. Alcohol Alcohol. 29:1994;663-671.
111. Smith T., DeMaster E.G., Furne J.K., Springfield J., Levitt M.D. First-pass gastric mucosal metabolism of ethanol is negligible in the rat. J. Clin. Invest. 89:1992;1801-1806.
112. Derr R.F. Simulation studies on ethanol metabolism in different human populations with a physiological pharmacokinetic model. J. Pharm. Sci. 82:1993;677-682.
113. Leinweber F.-J. Possible physiological roles of carboxylic ester hydrolases. Drug Metab. Dispos. 18:1987;379-439.
114. Inoue M., Morikawa M., Tsuboi M., Sugiura M. Species difference and characterization of intestinal esterase on the hydrolyzing activity of ester-type drugs. Jpn. J. Pharmacol. 29:1979;9-16.
115. Hosokawa M., Endo T., Fujisawa M., Hara S., Iwata N., Satao Y., Satoh T. Interindividual variation in carboxylesterase levels in human liver microsomes. Drug Metab. Dispos. 23:1995;1022-1027.
116. Williams F.M. Clinical significance of esterase in man. Clin. Pharmacokinet. 10:1985;392-403.
117. Williams F.M., Mutch E.M., Nicholson E., Wynne H., Wright P., Lambert D., Rawlins M.D. Human liver and plasma aspirin esterase. J. Pharm. Pharmacol. 41:1989;407-409.
118. Diczfaluzy E., Franksson C., Lisboa B.P., Martinsen B. Formation of oestrone glucosiduronate by the human intestinal tract. Acta. Endocrinol. 40:1962;537-551.
119. Back D.J., Bates M., Breckenridge A.M., Ellis A., Hall J.M., Maciver M., Orme M.L'E., Rowe P.H. The in vitro metabolism of ethinyloestradiol, mestranol and levonorgestrel by human jejunal mucosa. Br. J. Clin. Pharmacol. 11:1981;275-278.
120. D.J. Clarke, B. Burchell, The uridine diphosphate glucuronosyltransferase multigene family: function, and regulation, in: F.C. Kauffmann (Ed.), Conjugation-deconjugation reactions in drug metabolism and toxicity, Springer, Berlin, 1994, pp. 3-43.
121. Coffman B.L., Rios G.R., King C.D., Tephly T.R. Human UGT2B7 catalyzes morphine glucuronidation. Drug Metab. Dispos. 25:1997;1-4.
122. Ebner T., Remmel R.P., Burchell B. Human bilirubin UDP-glucuronosyltransferase catalyzes the glucuronidation of ethinylestradiol. Mol. Pharmacol. 43:1993;649-654.
123. Abdallah C., Besner J.G., Du Souich P. Presystemic elimination of morphine in anesthetized rabbits. Contribution of the intestine, liver, and lungs. Drug Metab. Dispos. 23:1995;584-589.
124. Ilett K.F., Tee L.B.G., Reeves P.T., Minchin R.F. Metabolism of drugs and other xenobiotics in the gut lumen and wall. Pharmacol. Ther. 46:1990;67-93.
125. Hickman D., Chandrasena G., Unadkat J. Longitudinal distribution of arylamine N-acetyltransferases along the human small intestine. ISSX Proc. 8:1995;250.
126. Pacifici G.M., Santerini S., Giuliani L. Methylation of captopril in human liver, kidney and intestine. Xenobiotica. 21:1991;1107-1112.
127. Pacifici G.M., Romiti P., Santerini S., Giuliani L. S-methyltransferases in human intestine: differential distribution of the microsomal thiol methyltransferase and cytosolic thiopurine methyltransferase along the human bowel. Xenobiotica. 23:1993;671-679.
128. Krynetski E.Y., Schuetz J.D., Galpin A.J., Pui C.-H., Relling M.V., Evans W.E. A single point mutation leading to loss of catalytic activity in human thiopurine S-methyltransferase. Proc. Natl. Acad. Sci. USA. 92:1995;949-953.
129. Kolars J.C., Awni W.M., Merion R.M., Watkins P.B. First-pass metabolism of cyclosporin by the gut. Lancet. 338:1991;1488-1490.
130. Gomez D.Y., Wacher V.J., Tomlanovich S.J., Hebert M.F., Benet L.Z. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin. Pharmacol. Ther. 58:1995;15-19.
131. Holtbecker N., Fromm M.F., Kroemer H.K., Ohnhaus E.E., Heidemann H. The nifedipine-rifampin interaction. Evidence for induction of gut wall metabolism. Drug Metab. Dispos. 24:1996;1121-1123.
132. Fabre G., Rahmani R., Placidi M., Combalbert J., Covo J., Cano J.-P., Coulange C., Ducros M., Rampal M. Characterization of midazolam metabolism using human hepatic microsomal fractions and hepatocytes in suspension obtained by perfusing whole human livers. Biochem. Pharmacol. 37:1988;4389-4397.
133. Kronbach T., Mathys D., Umeno M., Gonzalez F.J., Meyer U.A. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol. Pharmacol. 36:1989;89-96.
134. Paine M.F., Shen D.D., Kunze K.L., Perkins J.D., Marsh C.L., McVicar J.P., Barr D.M., Gillies B.S., Thummel K.E. First-pass metabolism of midazolam by the human intestine. Clin. Pharmacol. Ther. 60:1996;14-24.
135. Madsen J.L. Effects of gender, age, and body mass index on gastrointestinal transit times. Dig. Dis. Sci. 37:1992;1548-1553.
136. Fojo A.T., Ueda K., Slamon D.J., Poplack D.G., Gottesman M.M., Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc. Natl. Acad. Sci. USA. 84:1987;265-269.
137. van der Valk P., van Kalken C.K., Ketelaars H., Broxterman H.J., Scheffer G., Kuiper C.M., Tsuruo T., Lankelma J., Meijer C.J.L.M., Pinedo H.M., Scheper R.J. Distribution of multi-drug resistance-associated p-glycoprotein in normal and neoplastic tissues. Ann. Oncol. 1:1990;56-64.
138. Schuetz E.G., Schinkel A.H., Relling M.V., Schuetz J.D. P-glycoprotein: a major determinant of rifampin-inducible expression of cytochrome P4503A in mice and humans. Proc. Natl. Acad. Sci. USA. 93:1996;4001-4005.
139. Hosoya K.-I., Kim K.-J., Lee V.H.L. Age-dependent expression of p-glycoprotein gp170 in Caco-2 cell monolayers. Pharm. Res. 13:1996;885-890.
140. Fricker G., Drewe J., Huwyler J., Gutmann H., Beglinger C. Relevance of p-glycoprotein for the enteral absorption of cyclosporin A: in vitro-in vivo correlation. Br. J. Pharmacol. 118:1996;1841-1847.
141. Colburn W.A. A pharmacokinetic model to differentiate preabsorptive, gut epithelial, and hepatic first-pass metabolism. J. Pharmacokinet. Biopharm. 7:1979;407-415.
142. Klippert P.J.M., Noordhoek J. Influence of administration route and blood sampling site on the area under the curve. Assessment of gut wall, liver, and lung metabolism from a physiological model. Drug Metab. Dispos. 11:1983;62-66.
143. Mistry M., Houston J.B. Glucuronidation in vitro and in vivo. Comparison of intestinal and hepatic conjugation of morphine, naloxone, and buprenorphine. Drug Metab. Dispos. 15:1987;710-717.
144. Pond S.M., Tozer T.N. First-pass elimination. Basic concepts and clinical consequences. Clin. Pharmacokinet. 9:1984;1-25.
145. Klotz U., Ziegler G. Physiologic and temporal variation in hepatic elimination of midazolam. Clin. Pharmacol. Ther. 32:1982;107-112.
146. Stromberg C., Vanakoski J., Olkkola K.T., Lindqvist A., Seppala T., Laitinen L.A. Exercise alters the pharmacokinetics of midazolam. Clin. Pharmacol. Ther. 51:1992;527-532.
147. Gwilt P.R., Comer S., Chaturvedi P.R., Waters D.H. The influence of diffusional barriers on presystemic gut elimination. Drug Metab. Dispos. 16:1988;521-526.
148. Koster H., Mulder G.J. Apparent aberrancy in the kinetics of intracellular metabolism of a single substrate by the two enzymes. Drug Metab. Dispos. 10:1982;330-335.
149. De Lannoy I.A.M., Pang K.S. Effect of diffusional barriers on drug and metabolite kinetics. Drug Metab. Dispos. 15:1987;51-58.
150. Klippert P.J.M., Borm P., Noordhoek J. Prediction of intestinal first-pass of phenacetin in the rat from enzyme kinetic data - correlation with in vivo data using mucosal blood flow. Biochem. Pharmacol. 31:1982;2545-2548.
151. Xu X., Hirayama H., Pang K.S. First-pass metabolism of salicylamide. Studies in the once through vascularly perfused rat intestine-liver preparation. Drug Metab. Dispos. 17:1989;556-563.
152. Hirayama H., Pang K.S. First-pass metabolism of gentisamide: influence of intestinal metabolism on hepatic formation of conjugates. Studies in the once-through vascularly perfused rat intestine-liver preparation. Drug Metab. Dispos. 18:1990;580-587.
153. Chen J., Pang K.S. Effect of flow on first-pass metabolism of drugs: single pass studies on 4-methylumbelliferone conjugation in the serially perfused rat intestine and liver preparations. J. Pharmacol. Exper. Ther. 280:1997;24-31.
154. Park G.R., Manara A.R., Dawling S. Extrahepatic metabolism of midazolam. Br. J. Clin. Pharmacol. 27:1989;634-637.
155. Gray P.A., Park G.R., Cockshott I.D., Douglas E.J., Shuker B., Simons P.J. Propofol metabolism in man during the anhepatic and reperfusion phases of liver transplantation. Xenobiotica. 22:1992;105-114.
156. Veroli P., O'Kelly B., Bertrand F., Trouvin J.H., Farinotti R., Ecoffey C. Extrahepatic metabolism of propofol in man during the anhepatic phase of orthotopic liver transplantation. Br. J. Clin. Pharmacol. 68:1992;183-186.
157. Renwick A.G., Ahsan C.H., Challenor V.F., Daniels R., Macklin B.S., Waller D.G., George C.F. The influence of posture on the pharmacokinetics of orally administered nifedipine. Br. J. Clin. Pharmacol. 34:1992;332-336.
158. Drewe J., Beglinger C., Kissel T. The absorption site of cyclosporin in the human gastrointestinal tract. Br. J. Clin. Pharmacol. 33:1992;39-43.
159. Marathe P.H., Salazar D.E., Greene D.S., Brennan J., Shukla U.A., Barbhaiya R.H. Absorption and presystemic metabolism of nefazodone administered at different regions of the gastrointestinal tract of humans. Pharm. Res. 12:1995;1716-1721.
160. Warner P.E., Brouwer K.L.R., Hussey E.K., Dukes G.E., Heizer W.D., Donn K.H., Davies I.M., Powell J.R. Sumatriptan absorption from different regions of the human gastrointestinal tract. Pharm. Res. 12:1995;138-143.
161. Hulten L., Lindhagen J., Lundgren O. Sympathetic nervous control of intramural blood flow in the feline and human intestines. Gastroenterology. 72:1977;41-48.
162. W.S. Snyder, M.J. Cook, E.S. Nasset, L.R. Karhausen, G.P. Howells, I.H. Tipton, Report of the task group on reference man. International Commission on Radiological Protection, No. 23., Pergamon Press, Oxford, 1975, p. 136.
163. L.Z. Benet, S. Oie, J.B. Schwartz, Design and optimization of dosage regimens: pharmacokinetic data, in: J.G. Hardman, L.E. Limbard, P.B. Molinoff, R.W. Ruddon, A.G. Gilman (Eds.), The Pharmacological Basis of Therapeutics, Ninth Edition, McGraw-Hill, New York, 1996, pp. 1707-1792.
164. Fabre G., Julian B., Saint-Aubert B., Joyeux H., Berger Y. Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab. Dispos. 21:1993;978-985.
165. Schmider J., Greenblatt D.J., von Molkte L.L., Harmatz J.S., Shader R.I. N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors. J. Pharmacol. Exper. Ther. 275:1995;592-597.
166. Peyronneau M.-A., Delaforge M., Riviere R., Renaud J.-P., Mansuy D. High affinity of ergopeptides for cytochromes P450 3A. Importance of their peptide moiety for P450 recognition and hydroxylation of bromocriptine. Eur. J. Biochem. 223:1994;947-956.
167. Dahl M.-L., Bertilsson L. Genetically variable metabolism of antidepressants and neuroleptic drugs in man. Pharmacogenetics. 3:1993;61-70.
168. Mortimer O., Persson K., Ladona M.G., Spalding D., Zanger U.M., Meyer U.A., Rane A. Polymorphic formation of morphine from codeine in poor and extensive metabolizers of dextromethorphan: relationship to the presence of immunoidentified cytochrome P-450IID1. Clin. Pharmacol. Ther. 47:1990;27-35.
169. Caraco Y., Tateishi T., Guengerich F.P., Wood A.J.J. Microsomal codeine N-demethylation: cosegregation with cytochrome P4503A4 activity. Drug Metab. Dispos. 24:1996;761-764.
170. Kronbach T., Fisher V., Meyer U. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin. Pharmacol. Ther. 43:1988;630-635.
171. TB (CYP2C): a major monooxygenase catalyzing diclofenac 4′-hydroxylation in human liver. Life Sci. 52:1992;29-34.
172. Pichard L., Gillet G., Fabre I., Dalet-Beluche I., Bonfils C., Thenot J.-P., Maurel P. Identification of the rabbit and human cytochromes P-450IIIA as the major enzymes involved in the N-demethylation of diltiazem. Drug Metab. Dispos. 18:1990;711-719.
173. Guengerich F.P. Oxidation of 17α-ethynylestradiol by human liver cytochrome P-450. Mol. Pharmacol. 33:1988;500-508.
174. Guengerich F.P., Brian W.R., Iwasaki M., Sari M.-A., Baarnhielm C., Berntsson P. Oxidation of dihydropyridine calcium channel blockers and analogues by human liver cytochrome P-450 IIIA4. J. Med. Chem. 34:1991;1838-1844.
175. Lemoine A., Gautier J.C., Azoulay D., Kiffel L., Belloc C., Guengerich F.P., Maurel P., Beaune P., Leroux J.P. Major pathway of imipramine metabolism is catalyzed by cytochromes P-450 1A2 and P-450 3A4 in human liver. Mol. Pharmacol. 43:1993;827-832.
176. Bargetzi M.J., Aoyama T., Gonzalez F.J., Meyer U.A. Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4. Clin. Pharmacol. Ther. 46:1989;521-527.
177. Stearns R.A., Chakravarty P.K., Chen R., Chiu S.-H.L. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes. Role of cytochrome P4502C and 3A subfamily members. Drug Metab. Dispos. 23:1995;207-215.
178. Lo M.W., Goldberg M.R., McCrea J.B., Lu H., Furtek C.I., Bjornsson T.D. Pharmacokinetics of losartan, an angiotensin II receptor antagonist, and its active metabolite EXP3174 in humans. Clin. Pharmacol. Ther. 58:1995;641-649.
179. Wang R.W., Kari P.H., Lu A.Y.H., Thomas P.E., Guengerich F.P., Vyas K.P. Biotransformation of lovastatin. IV. Identification of cytochrome P450 3A proteins as the major enzymes responsible for the oxidative metabolism of lovastatin in rat and human liver microsomes. Arch. Biochem. Biophys. 290:1991;355-361.
180. Gut J., Catin T., Dayer P., Kronbach T., Zanger U., Meyer U.A. Debrisoquine/sparteine-type polymorphism of drug oxidation. J. Biol. Chem. 261:1986;11734-11743.
181. Otton S.V., Crewe H.K., Lennard M.S., Tucker G.T., Woods H.F. Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P450 in metoprolol oxidation by human liver microsomes. J. Pharmacol. Exper. Ther. 247:1988;242-247.
182. 14C] nefazodone in humans. Drug Metab. Dispos. 24:1996;91-95.
183. Guengerich F.P., Martin M.V., Beaune P.H., Kremers P., Wolff T., Waxman W.J. Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J. Biol. Chem. 261:1986;5051-5060.
184. Andersson T., Miners J.O., Veronese M.E., Tassaneeeyakul W., Tassaneeeyakul W., Meyer U.A., Birkett D.J. Identification of human liver P450 isoforms mediating omeprazole metabolism. Br. J. Clin. Pharmacol. 36:1993;521-531.
185. Kroemer H.K., Mikus G., Kronbach T., Meyer U.A., Eichelbaum M. In vitro characterization of the human cytochrome P-450 involved in polymorphic oxidation of propafenone. Clin. Pharmacol. Ther. 45:1989;28-33.
186. Masubichi Y., Hosokawa S., Horie T., Suzuki T., Ohmori S., Kitada M., Narimatsu S. Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes. The role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-deisopropylase. Drug Metab. Dispos. 22:1994;909-915.
187. 2 and cumene hydroperoxide-supported reactions. Drug Metab. Dispos. 24:1996;112-118.
188. Williams P.E.O., Muirhead G.J., Madigan M.J., Mitchell A.M., Shaw T. Disposition of bioavailability of the HIV-proteinase inhibitor, Ro 31-8959, after single oral doses in healthy volunteers. Br. J. Clin. Pharmacol. 34:1992;155P-156P.
189. Spaldin V., Madden S., Adams D.A., Edwards R.J., Davies D.S., Park B.K. Determination of human hepatic cytochrome P4501A2 activity in vitro. Use of tacrine as an isozyme-specific probe. Drug Metab. Dispos. 23:1995;929-934.
190. Sattler M., Guengerich F.P., Yun C.-H., Christians U., Sewing K.-Fr. Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab. Dispos. 20:1992;753-761.
191. Ling K.-H.J., Leeson G.A., Burmaster S.D., Hook R.H., Reith M.K., Cheng L.K. Metabolism of terfenadine associated with CYP3A(4) activity in human hepatic microsomes. Drug Metab. Dispos. 23:1995;631-636.
192. Okerholm R.A., Weiner D.L., Hook R.H., Walker B.J., Leeson G.A., Biedenbach S.A., Cawein M.J., Dusebout T.D., Wright G.J. Bioavailability of terfenadine in man. Biopharm. Drug Disp. 2:1981;185-190.
193. Garteiz D.A., Hook R.H., Walker B.J., Okerholm R.A. Pharmacokinetics and biotransformation studies of terfenadine in man. Arzneim.-Forsch./Drug Res. 32:1982;1185-1190.
194. Otton S.V., Ball S.E., Cheung S.W., Inaba T., Rudolph R.L., Sellers E.M. Venlafaxine oxidation in vitro is catalyzed by CYP2D6. Br. J. Clin. Pharmacol. 41:1996;149-156.
195. Kroemer H.K., Gautier J.-C., Beaune P., Henderson C., Wolff R., Eichelbaum M. Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn-Schmiedeberg's Arch. Pharmacol. 348:1993;332-337.
196. Busse D., Cosme J., Beaune P., Kroemer H.K., Eichelbaum M. Cytochromes of the P450 2C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn-Schmiedeberg's Arch. Pharmacol. 353:1995;116-121.
197. Sugihara J., Sugawara Y., Ando H., Harigaya S., Etoh A., Kohno K. Studies on the metabolism of diltiazem in man. J. Pharmacobiodyn. 7:1984;24-32.
198. Conoly M.E., Davies D.S., Dollery C.T., Morgan C.D., Paterson J.W., Sandler M. Metabolism of isoprenaline in dog and man. Br. J. Clin. Pharmacol. 46:1972;458-472.
199. Martin L.E., Hopkins R., Bland R. Metabolism of labetalol by animals and man. Br. J. Clin. Pharmacol. 3(Suppl. 3):1976;695-710.
200. Lillibridge J.A., Kalhorn T.F., Slattery J.T. Metabolism of lisofylline and pentoxifylline in human liver microsomes and cytosol. Drug Metab. Dispos. 24:1996;1174-1179.
201. Walle T., Walle U.K., Olanoff L.S. Quantitative account of propranolol metabolism in urine of normal man. Drug Metab. Dispos. 13:1985;204-209.
202. Karim A., Zagarella J., Hribar J., Dooley M. Spironolactone. I. Disposition and metabolism. Clin. Pharmacol. Ther. 19:1976;158-169.
203. Dixon C.M., Park G.R., Tarbit M.H. Characterization of the enzyme responsible for the metabolism of sumatriptan in human liver. Biochem. Pharmacol. 47:1994;1253-1257.
204. Tassaneeyakul W., Mohamed Z., Birkett D.J., McManus M.E., Veronese M.E., Tukey R.H., Quattrochi L.C., Gonzalez F.J., Miners J.O. Caffeine as a probe for human cytochromes P450: validation using cDNA-expression, immunoinhibition and microsomal kinetic and inhibitor techniques. Pharmacogenetics. 2:1992;173-183.
205. Fuhr U., Wolff T., Harder S., Schymanski P., Staib A.H. Quinolone inhibition of cytochrome P-450-dependent caffeine metabolism in human liver microsomes. Drug. Metab. Dispos. 18:1990;1005-1010.
206. Kunze K.L., Wienkers L.C., Thummel K.E., Trager W.F. Warfarin-fluconazole I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab. Dispos. 24:1996;414-420.
207. Chiba K., Kobayashi K., Manabe K., Tani M., Kamataki T., Ishizaki T. Oxidative metabolism of omeprazole in human liver microsomes: cosegregation with S-mephenytoin 4'-hydroxylation. J. Pharmacol. Exp. Ther. 226:1993;52-59.
208. Tyndale R.F., Inaba T., Kalow W. Evidence in humans for variant allozymes of the nondeficient sparteine/debrisoquine monooxygenase (P450IID1) in vitro. Drug Metab. Disp. 17:1989;334-340.
209. Peter R., Böcker R., Beaune P.H., Iwasaki M., Guengerich F.P., Yang C.S. Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1. Chem. Res. Toxicol. 3:1990;566-573.
210. Guengerich F.P., Muller-Enoch D., Blair I.A. Oxidation of quinidine by human liver cytochrome P-450. Mol. Pharmacol. 30:1986;287-295.
211. Lin J.H., Chiba M., Balani S.K., Chen I.-W., Kwei G.Y.-S., Vastag K.J., Nishime J.A. Species differences in the pharmacokinetics and metabolism of indinavir, a potent human immunodeficiency virus protease inhibitor. Drug Metab. Dispos. 24:1996;1111-1120.
212. Kerr B.M., Thummel K.E., Wurden C.J., Klein S.M., Kroetz D.L., Gonzalez F.J., Levy R.H. Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10,11-epoxide formation. Biochem. Pharmacol. 47:1994;1-11.
213. Shiraga T., Matsuda H., Nagase K., Iwasaki K., Noda K., Yamazaki H., Shimada T., Funae Y. Metabolism of FK506, a potent immunosuppressive agent, by cytochrome P450 3A enzymes in rat, dog and human liver microsomes. Biochem. Pharmacol. 47:1994;727-735.
214. Pichard L., Fabre I., Fabre G., Domergue J., Saint Aubert B., Mourad G., Maurel P. Cyclosporine A drug interactions. Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab. Dispos. 18:1990;595-606.
215. Rodrigues A.D., Mulford D.J., Lee R.D., Surber B.W., Kukulka M.J., Ferrero J.L., Thomas S.B., Shet M.S., Estabrook R.W. In vitro metabolism of terfenadine by a purified recombinant fusion protein containing cytochrome P4503A4 and NADPH-P450 reductase. Comparison to human liver microsomes and precision-cut liver tissue slices. Drug Metab. Dispos. 23:1995;765-775.