In vitro and in vivo drug interactions involving human CYP3A

Annual Review of Pharmacology and Toxicology

Volumn 38, Issue , 1998, Pages 389-430

  Thummel, K E ^a   Wilkinson, G R ^b  

^a UNIVERSITY OF WASHINGTON   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Drug metabolism; Enzyme induction; Enzyme inhibition; First pass metabolism

Indexed keywords

CLOTRIMAZOLE; CYTOCHROME P450; DEXAMETHASONE; ERYTHROMYCIN; FLUCONAZOLE; FLUOXETINE; GLYCOPROTEIN P; INDINAVIR; ITRACONAZOLE; JOSAMYCIN; MICONAZOLE; NELFINAVIR; NICARDIPINE; NIFEDIPINE; NORFLUOXETINE; NORSERTRALINE; PROGESTERONE; RITONAVIR; ROKITAMYCIN; SAQUINAVIR; SERTRALINE; TROLEANDOMYCIN; VERAPAMIL;

ANIMAL TISSUE; COMPETITIVE INHIBITION; DRUG METABOLISM; ENZYME INHIBITION; ENZYME SPECIFICITY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; IN VIVO STUDY; INTESTINE EPITHELIUM; NONHUMAN; PREDICTION; PRIORITY JOURNAL; REVIEW; TISSUE DISTRIBUTION;

ANIMALIA;

EID: 0031748173     PISSN: 00664251     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.pharmtox.38.1.389     Document Type: Review

References (279)

1. Maurel P. 1996. The CYP3 Family. In Cytochromes P450: Metabolic and Toxicological Aspects, ed. C Ioannides, pp. 241-70. Boca Raton, FL: CRC
2. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. 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 Caucasians. J. Pharmacol. Exp. Ther. 270:414-23
3. Kolars JC, Lown KS, Schmiedlin-Ren P, Ghosh M, Fang C, et al. 1994. CYP3A gene expression in human gut epithelium. Pharmacogenetics 4:247-59
4. McKinnon RA, Burgess WM, Hall P de la M, Roberts-Thomson SJ, Gonzalez FJ, McManus ME. 1995. Characterization of CYP3A gene subfamily expression in human gastrointestinal tissues. Gut 36:259-67
5. Schuetz EG, Schuetz JD, Grogan WM, Naray-Fejes-Toth A, Fejes-Toth G, et al. 1992. Expression of cytochrome P450 3A in amphibian, rat, and human kidney. Arch. Biochem. Biophys. 294:206-14
6. Haehner BD, Gorski JC, Vandenbranden M, Wrighton SA, Janardan SK, et al. 1996. Bimodal distribution of renal cytochrome P450 3A activity in humans. Mol. Pharmacol. 50:52-59
7. Wrighton SA, Ring BJ, Watkins PB, Vandenbranden M. 1989. Identification of a polymorphically expressed member of the human cytochrome P-450III family. Mol. Pharmacol. 36:97-105
8. Wrighton SA, Brian WR, Sari MA, Iwasaki M, Guengerich FP, et al. 1990. Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol. Pharmacol. 38:207-13
9. Jounaïdi Y, Hyrailles V, Gervot L, Maurel P. 1996. Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein? Biochem. Biophys. Res. Commun. 221:466-70
10. Gervot L, Carrière V, Costet P, Cugnenc P-H, Berger A, et al. 1996. CYP3A5 is the major cytochrome P450 3A expressed in human colon and colonic cell lines. Environ. Tox. Pharmacol. 2:381-88
11. Schuetz EG, Schuetz JD, Strom SC, Thompson MT, Fisher RA, et al. 1993. Regulation of human liver cytochromes P-450 in family 3 A in primary and continuous culture of human hepatocytes. Hepatology 18:1254-62
12. Schuetz JD, Beach DL, Guzelian PS. 1994. Selective expression of cytochrome P450 CYP3A mRNAs in embroyonic and adult human liver. Pharmacogenetics 4:11-20
13. Guengerich FP. 1995. Human cytochrome P450 enzymes. In Cytochrome P450: Structure, Mechanism, and Biochemistry, ed. PR Ortiz de Montellano, pp. 473-535. New York: Plenum
14. Aoyama T, Yamano S, Waxman DJ, Lapenson DP, Meyer UA, et al. 1989. Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J. Biol. Chem. 264:10388-95
15. Gorski JC, Hall SD, Jones DR, Vandenbranden M, Wrighton SA. 1994. Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem. Pharmacol. 47:1643-53
16. Lown KS, Kolars JC, Thummel KE, Barnett JL, Kunze KL, et al. 1994. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel -lack of prediction by the erythromycin breath test. Drug Metab. Disp. 22:947-55
17. Gottesman MM, Pastan I. 1993. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem. 62: 385-427
18. Wacher VJ, Wu CY, Benet LZ. 1995. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinogen. 13:129-34
19. Kivistö KT, Kroemer HK, Eichelbaum M. 1995. The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions. Br. J. Clin. Pharmacol. 40:523-30
20. Hunter J, Hirst BH, Simmons NL. 1993. Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm. Res. 10:743-49
21. Leu B-L, Huang J-D. 1995. Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother. Pharmacol. 35:432-36
22. Terao T, Hisanaga E, Sai Y, Tamai I, Tsuji A. 1996. Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J. Pharm. Pharmacol. 48:1083-89
23. Schuetz EG, Schinkel AH, Relling MV, Schuetz JD. 1996. P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans. Proc. Natl. Acad. Sci. USA 93:4001-5
24. Skett P, Tyson C, Guillouzo A, Maier P. 1995. Report on the international workshop on the use of human in vitro liver preparations to study drug metabolism in drug development. Biochem. Pharmacol. 50:280-85
25. Rodrigues AD. 1994. Use of in vitro human metabolism studies in drug development - an industrial perspective. Biochem. Pharmacol. 48:2147-56
26. Watkins PB, Wrighton SA, Schuetz EG, Maurel P, Guzelian PS. 1986. Macrolide antibiotics inhibit the degradation of the glucocorticoid-responsive cytochrome P-450p in rat hepatocytes in vivo and in primary monolayer culture. J. Biol. Chem. 261:6264-71
27. Shaw PM, Barnes TS, Cameron D, Engeset J, Melvin WT, et al. 1989. Purification and characterization of an anticonvulsant-induced human cytochrome P-450 catalysing cyclosporin metabolism. Biochem. J. 263:653-63
28. Thummel KE, Shen DD, Podoll T, Kunze KL, Trager WF, et al. 1994. Use of midazolam as a human cytochrome P450 3A probe: II. Characterization of inter- and intra-individual hepatic P450 3 A variability after liver transplantation. J. Pharmacol. Exp. Ther. 271:557-66
29. Kolars JC, Schmiedlin-Ren P, Schuetz JD, Fang C, Watkins PB. 1992. Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J. Clin. Invest. 90:1871-78
30. Wu C-Y, Benet LZ, Hebert MF, Gupta SK, Rowland M, et al. 1995. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin. Pharmacol. Ther. 58:492-97
31. Dou M, Desousa G, Lacarelle B, Placidi M, de la Porte PL, et al. 1992. Thawed human hepatocytes in primary culture. Cryobiology 29:454-69
32. Pearce RE, McIntyre CJ, Madan A, Sanzgiri U, Draper AJ, et al. 1996. Effects of freezing, thawing, and storing human liver microsomes on cytochrome P450 activity. Arch. Biochem. Biophys. 331:145-69
33. Yamazaki H, Inoue K, Turvey CG, Guengerich FP, Shimada T. 1997. Effects of freezing, thawing, and storage of human liver samples on the microsomal contents and activities of cytochrome P450 enzymes. Drug Metab. Dispos. 25:168-74
34. Vickers AE, Fisher RL, Brendel K, Guertler J, Dannecker R, et al. 1995. Sites of biotransformation for the cyclosporin derivative SDZ IMM 125 using human liver and kidney slices and intestine. Comparison with rat liver slices and cyclosporin A metabolism. Drug Metab. Dispos. 23:327-33
35. Vickers AE, Fisher V, Connors S, Fisher RL, Baldeck JP, et al. 1992. Cyclosporin A metabolism in human liver, kidney, and intestine slices. Comparison to rat and dog slices and human cell lines. Drug Metab. Dispos. 20:802-9
36. Rodrigues AD, Mulford DJ, Lee RD, Surber BW, Kukulla MJ, et al. 1995. 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. 23:765-75
37. Abdel-Razzak Z, Loyer P, Fautrel A, Gautier JC, Corcos L, et al. 1993. Cytokines down-regulate expression of major cytochrome P-450 enzymes in adult human hepatocytes in primary culture. Mol. Pharmacol. 44:707-15
38. Pichard L, Fabre I, Fahre G, Domergue J, Saint Aubert B, et al. 1990. Cyclosporine A drug interactions. Screening for inducers and inhibitors of cytochrome P450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab. Dispos. 18:595-606
39. Maurice M, Pichard L, Daujat M, Fabre I, Joyeux H, et al. 1992. Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J. 6:752-58
40. Donato MT, Castell JV, Gomez-Lechon MJ. 1995. Effect of model inducers on cytochrome P450 activities of human hepatocytes in primary culture. Drug Metab. Dispos. 23:553-58
41. Crespi CL, Penman BW, Hu M. 1996. Development of Caco-2 cells expressing high levels of cDNA-derived cytochrome P4503A4. Pharm. Res. 13:1635-41
42. Schmiedlin-Ren P, Thummel KE, Fisher JM, Paine MF, Lown KS, et al. 1997. Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1α, 25-dihydroxyvitamin D3. Mol. Pharmacol. 51:741-54
43. Ball SE, Maurer G, Zollinger M, Ladona M, Vickers AEM. 1992. Characterization of the cytochrome P-450 gene family responsible for the N-dealkylation of the ergot alkaloid CQA 206-291 in humans. Drug Metab. Dispos. 20:56-63
44. Brian WD, Sari M-A, Iwasaki M, Shimada T, Kaminsky LS, Guengerich FP. 1990. Catalytic activities of human liver cytochrome P-450 IIIA4 expressed in Saccharomyces cerevisiae. Biochemistry 29:11280-92
45. Renaud J-P, Cullin C, Pompon D, Beaune P, Mansuy D. 1990. Expression of human liver cytochrome P450 IIIA4 in yeast - a functional model for the hepatic enzyme. Eur. J. Biochem. 194:889-96
46. Gillam EMJ, Baba T, Kim B-R, Ohmori S, Guengerich FP. 1993. Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch. Biochem. Biophys. 305:123-31
47. Yamazaki H, Inui Y, Wrighton SA, Guengerich FP, Shimada T. 1995. Procarcinogen activation by cytochrome P450 3A4 and 3A5 expressed in Escherichia coli and by human liver microsomes. Carcinogenesis 16:2167-70
48. Buters JTM, Korzekwa KR, Kunze KL, Omata Y, Hardwick JP, Gonzalez FJ. 1994. cDNA-directed expression of human cytochrome P450 CYP3A4 using baculovirus. Drug Metab. Dispos. 22:688-92
49. Rauschenbach R, Gieschen H, Husemann M, Salomon B, Hildebrand M. 1995. Stable expression of human cytochrome P450 3A4 in V79 cells and its application for metabolic profiling of ergot derivatives. Eur. J. Pharmacol. 293:183-90
50. Schneider A, Schmalix WA, Siruguri V, deGroene EM, Horbach GJ, et al. 1996. Stable expression of human cytochrome P450 3A4 in conjunction with human NADPH-cytochrome P450 oxidoreductase in V79 Chinese hamster cells. Arch. Biochem. Biophys. 332:295-304
51. Crespi CL, Penman BW, Steimel DT, Gelboin HV, Gonzalez FJ. 1991. The development of a human cell line stably expressing human CYP3A4: role in the metabolic activation of aflatoxin B1 and comparison to CYP1A2 and CYP2A3. Carcinogenesis 12:355-59
52. Kitamura R, Sato K, Sawada M, Itoh S, Kitada M, et al. 1992. Stable expression of cytochrome P450IIIA7 cDNA in human breast cancer cell line MCF-7 and its application to cytotoxicity testing. Arch. Biochem. Biophys. 292:136-40
53. Peyronneau MA, Renaud JP, Truan G, Urban P, Pompon D, Mansuy D. 1992. Optimization of yeast-expressed human liver cytochrome P450 3A4 catalytic activities by coexpressing NADPH-cytochrome P450 reductase and cytochrome b5. Eur. J. Biochem. 207:109-16
54. Lee CA, Kadwell SH, Kost TA, Serabjit-Singh CJ. 1995. CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4. Arch. Biochem. Biophys. 319:157-67
55. Shet MS, Fisher CW, Holmans PL, Estabrook RW. 1993. Human cytochrome P450 3A4: enzymatic properties of a purified recombinant fusion protein containing NADPH-P450 reductase. Proc. Natl. Acad. Sci. USA 90:11748-52
56. Guengerich FP, Martin MV, Beaune PH, Kremers P, Wolff T, Waxman DJ. 1986. 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. 261:5051-60
57. Imaoka S, Imai Y, Shimada T, Funae Y. 1992. Role of phospholipids in reconstituted cytochrome P450 3A form and mechanism of their activation of catalytic activity. Biochemistry 31:6063-69
58. Ingelman-Sundberg M, Hagbjörk AL, Ueng YF, Yamazaki H, Guengerich FP. 1996. High rates of substrate hydroxylation by human cytochrome P450 3A4 in reconstituted membranous vesicles: influence of membrane change. Biochem. Biophys. Res. Commun. 221:318-22
59. Gillam EM, Guo Z, Ueng YF, Yamazaki H, Cock I, et al. 1995. Expression of cytochrome P450 3A5 in Escherichia coli: effects of 5′ modification, purification, spectral characterization, reconstitution conditions, and catalytic activities. Arch. Biochem. Biophys. 317:374-84
60. Yamazaki H, Ueng YF, Shimada T, Guengerich FP. 1995. 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. Biochemistry 34:8380-89
61. 5. J. Biol. Chem. 271:27438-44
62. Schmucker DL, Woodhouse KW, Wang RK, Wynne H, James OF, et al. 1990. Effects of age and gender on in vitro properties of human microsomal monoxygenases. Clin. Pharmacol. Ther. 48:365-74
63. Fabre G, Rahmani R, Placidi M, Combalbert J, Covo J-P, et al. 1988. Characterization of midazolam metabolism using human hepatic microsomal fractions and hepatocytes in suspension obtained by perfusing whole human livers. Biochem. Pharmacol. 37:4389-97
64. Paine MF, Khalighi M, Fisher JM, Shen DD, Kunze KL, et al. 1997. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J. Pharmacol. Exp. Ther. 283:1552-62
65. Shou M, Grogan J, Mancewicz JA, Krausz KW, Gonzalez FJ, et al. 1994. Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 33:6450-55
66. Ueng Y-F, Kuwabara T, Chun Y-J, Guengerich FP. 1997. Cooperativity in oxidations catalyzed by cytochrome P450 3A4. Biochemistry 36:370-81
67. Kerlan V, Dreano Y, Bercovici JP, Beaune PH, Floch HH, Berthou F. 1992. Nature of cytochromes P450 involved in the 2/4-hydroxylations of estradiol in human liver microsomes. Biochem. Pharmacol. 44:1745-56
68. Kerr BM, Thummel KE, Wurden CJ, Klein SM, Kroetz DL, et al. 1994. Human liver carbamazepine metabolism. Role of CYP3A4 and CYP2C8 in 10, 11-epoxide formation. Biochem. Pharmacol. 47:1969-79
69. Kronbach T, Mathys D, Umeno M, Gonzalez FJ, Meyer UA. 1989. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol. Pharmacol. 36:89-96
70. Yun CH, Wood M, Wood AJJ, Guengerich FP. 1992. Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4. An explanation of the variable elimination clearance. Anesthesiology 77:467-74
71. Raney KD, Shimada T, Kim DH, Groopman JD, Harris TM, Guengerich FP. 1992. Oxidation of aflatoxins and sterigmatocystin by human liver microsomes: significance of aflatoxin Q1 as a detoxication product of aflatoxin B1. Chem. Res. Toxicol. 5:202-10
72. Ueng YF, Shimada T, Yamazaki H, Guengerich FP. 1995. Oxidation of aflatoxin B1 by bacterial recombinant human cytochrome P450 enzymes. Chem. Res. Toxicol. 8:218-25
73. Lasker JM, Huang M-T, Conney AH. 1982. In vivo activation of zoxazolamine metabolism by flavone. Science 216:1419-21
74. Koley AP, Robinson RC, Friedman FK. 1996. Cytochrome P450 conformation and substrate interactions as probed by CO binding kinetics. Biochimie 78:706-13
75. Koley AP, Buters JTM, Robinson RC, Markowitz A, Friedman FK. 1995. CO binding kinetics of human cytochrome P450 3A4. J. Biol. Chem. 270:5014-18
76. Koley AP, Robinson RC, Markowtiz A, Friedman FK. 1997. Drug-drug interactions: effect of quinidine on nifedipine binding to human cytochrome P4503A4. Biochem. Pharmacol. 53:455-60
77. Lewis DFV, Eddershaw PJ, Goldfarb PS. Tarbit MH. 1996. Molecular modelling of CYP3A4 from an alignment with CYP102: identification of key interactions between putative active site residues and CYP3A-specific chemicals. Xenobiotica 26:1067-86
78. Bertz RJ, Granneman GR. 1997. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin. Pharmacokinet. 32:210-58.
79. Leemann TD, Dayer P. 1995. Quantitative prediction of in vivo drug metabolism and interactions from in vitro data. In Advances in Drug Metabolism in Man, ed. GM Pacifici, GN Fracchia, pp. 783-830. Brussels: Eur. Commis.
80. Gibbs MA, Thummel KE, Kunze KL. 1997. Differential inhibition of CYP3A and CYP3A5 by antifungal agents. ISSX Proc. 12:157
81. Bourrié M, Meunier V, Berger Y, Fabre G. 1996. Cytochrome P450 isoforms inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J. Pharmacol. Exp. Ther. 277:321-32
82. Wrighton SA, Ring BJ. 1994. Inhibition of human CYP3A catalyzed 1′-hydroxymidazolam formation by ketoconazole nifedipine, erythromycin, cimetidine, and nizatidine. Pharm. Res. 11:921-24
83. Lampen A, Christians U, Gungerich FP, Watkins PB, et al. 1995. Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability. Drug Metab. Dispos. 23:1315-24
84. von Moltke LL, Greenblatt DJ, Schmider J, Duan SX, Wright CE, et al. 1996. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J. Clin. Pharmacol. 36:783-91
85. Kunze KL, Wienkers LC, Thummel KE, Trager WF. 1996. Warfarin-fluconazole. I. Inhibition of the human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab. Dispos. 24:414-21
86. Kumar GN, Rodrigues AD, Buko AM, Denissen JF. 1996. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J. Pharmacol. Exp. Ther. 277:423-31
87. Fitzsimmons ME, Collins JM. 1997. Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4. Drug Metab. Dispos. 25:256-66
88. Wu EY, Sandoval TM, Lee CA, Zhang K, Liang BH, et al. 1996. In vitro metabolism studies with the HIV-1 protease inhibitor, Viracept (AG 1343). ISSX Proc. 10:326
89. Marre F, de Sousa G, Orloff AM, Rahmani R. 1993. In vitro interaction between cyclosporin A and macrolide antibiotics. Br. J. Clin. Pharmacol. 35:447-48
90. Zhou X-J, Zhou-Pan X-R, Gauthier T, Placidi M, Maurel P, Rahmani R. 1993. Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug reactions. Biochem. Pharmacol. 45:853-61
91. Ring BJ, Binkley SN, Roskos L, Wrighton SA. 1995. Effect of fluoxetine, norfluoxetine, sertraline and desmethylsertraline on human CYP3A catalyzed 1′-hydroxy midazolam formation in vitro. J. Pharmacol. Exp. Ther. 275:1131-35
92. von Molkte LL, Greenblatt DJ, Cortreau-Bibbo MM, Harmatz JS, Shader RI. 1994. Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br. J. Clin. Pharmacol. 38:23-31
93. Guengerich FP, Müller-Enoch D, Blair IA. 1986. Oxidation of quinidine by human liver cytochrome P-450. Mol. Pharmacol. 30:287-95
94. Gorski JC, Jones DR, Wrighton SA, Hall SD. 1994. Characterization of dextromethorphan N-demethylation by human liver microsomes, contribution of the cytochrome P450 3A(CYP3A) subfamily. Biochem. Pharmacol. 48:173-82
95. Ring BJ, Parli CJ, George MC, Wrighton SA. 1994. In vitro metabolism of zatosetron interspecies comparison and role of CYP3A. Drug Metab. Dispos. 22:352-57
96. Combalbert J, Fabre I, Fabre G, Dalet I, Derancourt J, et al. 1989. Metabolism of cyclosporin A. IV. Purification and identification of the rifampicin-inducible human liver cytochrome P-450 (cyclosporin A oxidase) as a product of P450IIIA gene subfamily. Drug Metab. Dispos. 17:197-207
97. Wrighton SA, Maurel P, Schuetz EG, Watkins PB, Young B, Guzelian PS. 1985. Identification of the cytochrome P-450 induced by macrolide antibiotics in rat liver as the glucocorticoid responsive cytochrome P-450p. Biochemistry 24:2171-78
98. Watkins PB, Wrighton SA, Maurel P, SchuetzEG, Mendez-Picon G, et al. 1985. Identification of an inducible form of cytochrome P-450 in human liver. Proc. Natl. Acad. Sci. USA 82:6310-14
99. Pessayre D, Descatoire V, Konstantinova-Mitcheva M, Wandscheer J-C, Cobert B, et al. 1981. Self-induction by triacetyloleandomycin of its own transformation into a metabolite forming a stable 456 nm-absorbing complex with cytochrome P-450. Biochem. Pharmacol. 30:553-58
100. Miura T, Iwasaki M, Komori M, Ohi H, Kitada M. 1989. Decrease in a constitutive form of cytochrome P-450 by macrolide antibiotics. J. Antimicrob. Chemother. 24:551-59
101. Babany G, Larrey D, Pessayre D. 1988. Macrolide antibiotics as inducers and inhibitors of cytochrome P-450 in experimental animals and man. In Progress in Drug Metabolism, ed. GG Gibson, 11:61-98. London: Taylor & Francis
102. Tinel M, Descatoire V, Larrey D, Loeper J, Labbe G, et al. 1989. Effects of clarithromycin on cytochrome P-450. Comparison with other macrolides. J. Pharmacol. Exp. Ther. 250:746-51
103. Ohmori S, Ishii I, Kuriya SI, Taniguchi T, Rikihisa T, et al. 1993. Effects of clarithromycin and its metabolites on the mixed function oxidase system in hepatic microsomes of rats. Drug Metab. Dispos. 21:358-63
104. Lindstrom TD, Hanssen BR, Wrighton. 1993. Cytochrome P-450 complex formation by dirithromycin and other macrolides in rat and human livers. Antimicrob. Agents Chemother. 37:265-69
105. Franklin MR. 1995. Enhanced rates of cytochrome P450 metabolic-intermediate complex formation from nonmacrolide amines in rifampicin-treated rabbit liver microsomes. Drug Metab. Dispos. 23: 1379-82
106. Bensoussan C, Delaforge M, Mansuy D. 1995. Particular ability of cytochrome P450 3A to form inhibitory P450-iron-metabolite complexes upon metabolic oxidation of aminodrugs. Biochem. Pharmacol. 49:591-602
107. Murray M, Field SL. 1992. Inhibition and metabolite complexation of rat hepatic microsomal cytochrome P450 by tricyclic antidepressants. Biochem. Pharmacol. 43:2065-71
108. Witkamp RF, Nijmeijer SM, Monshouwer M, van Miert SJPAM. 1995. The antibiotic tiamulin is a potent inducer and inhibitor of cytochrome P4503A via the formation of a stable metabolic intermediate complex. Studies in primary hepatocyte cultures and liver microsomes of the pig. Drug Metab. Dispos. 23:542-47
109. Larrey D, Tinel M, Letteron P, Geneve J, Descatoire V, et al. 1986. Formation of an inactive cytochrome P-450Fe(II)-metabolite complex after administration of amiodarone in rats, mice and hamsters. Biochem. Pharmacol. 35:2213-20
110. Shaeffer MS, Collier D, Sorrell MF. 1994. Interaction between FK506 and erythromycin. Ann. Pharmacother. 28:280-81
111. Ludden TM. 1985. Pharmacokinetic interactions of the macrolide antibiotics. Clin. Pharmacokinet. 10:63-79
112. Campana C, Regazzi MB, Buggia I, Molinaro M. 1996. Clinically significant drug interactions with cyclosporin. Clin. Pharmacokinet. 30:141-79
113. Honig PK, Woosley RL, Zamani K, Conner DR, Cantilena LP. 1992. Changes in the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine with concomitant administration of erythromycin. Clin. Pharmacol. Ther. 52:231-38
114. Gray MR, Tam YK. 1991. Pharmacokinetics of drugs that inactivate metabolic enzymes. J. Pharmaceut. Sci. 80:121-27
115. Guengerich FP. 1988. Oxidation of 17α-ethynylestradiol by human liver cytochrome P-450. Mol. Pharmacol. 33:500-8
116. Guengerich FP. 1990. Mechanism-based inactivation of human liver microsomal cytochrome P-450 IIIA4 by gestodene. Chem. Res. Toxicol. 3:363-71
117. Sahali-Sahly Y, Balani SK, Lin JH, Baillie TA. 1996. In vitro studies on the metabolic activation of the furanopyridine L-754,394, a highly potent and selective mechanism-based inhibitor of cytochrome P450 3A4. Chem. Res. Toxicol. 9:1007-12
118. Bailey DG, Arnold JMO, Spence JD. 1994. Grapefruit juice and drugs - how significant is the interaction? Clin. Pharmacokinet. 26:91-98
119. Wilkinson GR. 1997. The effects of diet, aging and disease-states on presystemic elimination and oral drug bioavailability in humans. Adv. Drug Deliv. Rev. 27:129-59
120. Schmiedlin-Ren P, Edwards DJ, Fitzsimmons ME, He K, Lown KS, et al. 1997. Mechanisms of enhanced oral availability of CYP3A substrates by grapefruit constituents: decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins. Drug Metab. Dispos. 25:1228-33
121. Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, et al. 1997. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J. Clin. Invest. 99:2545-53
122. Edwards DJ, Bellevue FH III, Woster PM. 1996. Identification of 6′, 7′-dihydroxybergamottin, a cytochrome P450 inhibitor, in grapefruit juice. Drug. Metab. Dispos. 24:1287-90
123. Delaforge M, Ladam P, Bouillé G, Benarous J, Jaouen M, et al. 1992. pH effects on the N-demethylation and formation of the cytochrome P-450 iron II nitrosoalkane complex for erythromycin derivatives. Chem. Biol. Interact. 85:215-27
124. Wang RW, Newton DJ, Seheri TD, Lu AY. 1997. Human cytochrome P450 3A4-catalyzed testosterone 6β-hydroxylation and erythromycin N-demethylation. Drug Metab. Dispos. 25:502-7
125. Obach RS. 1996. The importance of non-specific binding in in vitro matrices, its impact on enzyme kinetic studies of drug metabolism reactions, and implications for in vitro-in vivo correlations. Drug Metab. Dispos. 24:1047-49
126. Obach RS. 1997. Non-specific binding to microsomes: impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine, and propranolol. Drug Metab. Dispos. 25:1359-69
127. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS, et al. 1994. 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. 268:1278-83.
128. von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, et al. 1996. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors and clinical confirmation of a predicted interaction with ketoconazole. J. Pharmacol. Exp. Ther. 276:370-79
129. von Moltke LL, Greenblatt DJ, Schmider J, Duan SX, Wright CE, et al. 1996. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antirungalagents. J. Clin. Pharmacol. 36:783-91
130. Yeung PKF, Buckley SJ, Hung OR, Pollak PT, Barclay KD, et al. 1996. Steady-state plasma concentrations of diltiazem and its metabolites in patients and healthy volunteers. Ther. Drug Monit. 18:40-45
131. Backman JT, Olkkola KT, Aranko K, Himberg J-J, Neuvonen PJ. 1994. Dose of midazolam should be reduced during diltiazem and verapamil treatments. Br. J. Clin. Pharmacol. 37:221-25
132. Varhe A, Olkkola KT, Neuvonen PJ. 1996. Diltiazem enhances the effects of triazolam by inhibiting its metabolism. Clin. Pharmacol. Ther. 59:369-75
133. Shum L, Pieniaszek HJ Jr, Robinson CA, Davidson AF, Widner PJ, et al. 1996. Pharmacokinetic interactions of moricizine and diltiazem in healthy volunteers. J. Clin. Pharmacol. 36:1161-68
134. Laganière S, Davies RF, Carignan G, Foris K, Goernert L, et al. 1996. Pharmacokinetic and pharmacodynamic interactions between diltiazem and quinidine. Clin. Pharmacol. Ther. 60:255-64
135. Spina E, Pisani F, Perucca E. 1996. Clinically significant pharmacokinetic drug interactions with carbamazepine. An up-date. Clin. Pharmacokinet. 31:198-214
136. Ohashi K, Sakamoto K, Sudo T, Tateishi T, Fujimura A, et al. 1993. Effects of diltiazem and cimetidine on theophylline oxidative metabolism. J. Clin. Pharmacol. 33:1233-37
137. Ahonen J, Olkkola KT, Salmenperä M, Hynynen M, Neuvonen PJ. 1996. Effect of diltiazem on midazolam and alfentanil disposition in patients undergoing coronary artery bypass grafting. Anesthesiology 85:1246-52
138. Gomez DY, Wacher VJ, Tomlanovich SJ, Herbert MF, Benet LZ. 1995. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin. Pharmacol. Ther. 58:15-29
139. Olkkola KT, Ahonen J, Neuvonen PJ. 1996. The effect of the systemic antimycotics, intraconazole and fluconazole, on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth. Analg. 82:511-16
140. Wienkers LC, Steenwyk RC, Sanders PE, Pearson PG. 1996. Biotransformation of tirilazad in human: 1. Cytochrome P450 3A-mediated hydroxylation of tirilazad mesylate in human liver microsomes. J. Pharmacol. Exp. Ther. 277:982-90
141. Fleishaker JC, Pearson PG, Wienkers LC, Pearson LK, Peters GR. 1996. Biotransformation of tirilazad in human: 2. Effect of ketoconazole on tirilazad clearance and oral bioavailability. J. Pharmacol. Exp. Ther. 277:991-98
142. Siegsmund MJ, Cardarelli C, Aksentijevich I, Sugimoto Y, Pastan I, Gottesman MM. 1994. Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. J. Urol. 15:485-91
143. Vanakoski J, Mattila MJ, Vainio P, Idänpään-Heikkilä JJ, Törnwall M. 1995. 150 mg fluconazole does not substantially increase the effects of 10 mg midazolam or the plasma midazolam concentrations in healthy subjects. Int. J. Clin. Pharmacol. Ther. 33:518-23
144. Ahonen J, Olkkola KT, Neuvonen PJ. 1997. Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. Eur. J. Clin. Pharmacol. 51:415-19
145. Black DJ, Kunze KL, Wienkers LC, Gidal BE, Seaton TL, et al. 1996. Warfarinfluconazole. II. A metabolically based drug interaction: in vivo studies. Drug Metab. Dispos. 24:422-28
146. Morel F, Beaune P, Ratanasavanh D, Flinois JP, Yang CS, et al. 1990. Expression of cytochrome P450 enzymes in cultured human hepatocytes. Eur. J. Biochem. 191:437-44
147. Pichard L, Fabre I, Daujat M, Domergue J, Joyeux H, Maurel P. 1992. Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. Mol. Pharmacol. 41:1047-55
148. Daujat M, Clair P, Astier C, Fabre I, Pineau T, et al. 1991. Induction, regulation and messenger half-life of cytochromes P450 IA1, IA2, and IIIA6 in primary cultures of rabbit hepatocytes. 1A1, 1A2 and 3A6 chromosome location in the rabbit and evidence that post-transcriptional control of gene IA2 does not involve mRNA stabilization. Eur. J. Biochem. 200:501-10
149. Telhada MB, Pereira TM, Lechner MC. 1992. Effect of dexamethasone and phenobarbital on run-on transcription rate and CYP3A mRNA concentration in rat liver: changes during development. Arch. Biochem. Biophys. 298:715-25
150. Schuetz EG, Wrighton SA, Safe SH, Guzelian PS. 1986. Regulation of cytochrome P-450p by phenobarbital and phenobarbital-like inducers in adult rat hepatocytes in primary monolayer culture and in vivo. Biochemistry 25:1124-33
151. Gonzalez FJ, Song BJ, Hardwick JP. 1986. Pregnenolone 16α-carbonitrile-inducible P-450 gene family: gene conversion and differential regulation. Mol. Cell. Biol. 6:2969-76
152. Molowa DT, Schuetz EG, Wrighton SA, Watkins PB, Kremers P, et al. 1986. Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc. Natl. Acad. Sci. USA 83:5311-15
153. Li AP, Rasmussen A, Xu L, Kaminski DL. 1995. Rifampicin induction of lidocaine metabolism in cultured human hepatocytes. J. Pharmacol. Exp. Ther. 274:673-77
154. Hashimoto H, Toide K, Kitamura R, Fujita M, Tagawa S, et al. 1993. Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control. Eur. J. Biochem. 218:585-95
155. Schuetz JD, Schuetz EG, Thottassery JV, Guzelian PS, Strom S, Sun D. 1996. Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells. Mol. Pharmacol. 49:63-72
156. Wright MC, Wang X-J, Pimenta M, Ribeiro V, Paine AJ, et al. 1996. Glucocorticoid receptor-independent transcriptional induction of cytochrome P450 3A1 by metyrapone and its potentiation by glucocorticoid. Mol. Pharmacol. 50:856-63
157. Schuetz EG, Schuetz JD, May B, Guzelian PS. 1990. Regulations of cytochrome P-450b/e and P-450p gene expression by growth hormone in adult rat hepatocytes cultured on a reconstituted basement membrane. J. Biol. Chem. 265:1188-92
158. Waxman DJ. 1988. Interactions of hepatic cytocnromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression. Biochem. Pharmacol. 37:71-84
159. Eliasson E, Mkrtchian S, Halpert JR, Ingelman-Sundberg M. 1994. Substrate-regulated, cAMP-dependent phosphorylation, denaturation, and degradation of glucocorticoid-inducible rat liver cytochrome P450 3A1. J. Biol. Chem. 269: 18378-83
160. Watkins PB, Murray SA, Winkelman LG, Heuman DM, Wrighton SA, Guzelian PS. 1989. Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450. Studies in rats and patients. J Clin. Invest. 83:688-97
161. Olkkola KT, Aranko K, Luurila H, Hiller A, Saarnivaara L, et al. 1993. A potentially hazardous interaction between erythromycin and midazolam. Clin. Pharmacol. Ther. 53:298-305
162. Mattila MJ, Heikkilä JJI, Törnwall M, Vanakoski J. 1993. Oral single doses of erythromycin and roxithromycin may increase the effects of midazolam on human performance. Pharmacol. Toxicol. 73:180-85
163. Jones DR, Gorski C, Haehner BD, O'Mara EM, Hall SD. 1996. Determination of cytochrome P450 3A4/5 activity in vivo with dextromethorphan N-demethylation. Clin. Pharmacol. Ther. 60:374-84
164. Kharasch ED, Russell M, Mautz D, Thummel KE, Kunze KL, et al. 1997. The role of cytochrome P450 3A4 in alfentanil clearance: implications for interindividual variability in disposition and perioperative drug interactions. Anesthesiology 87:36-50
165. Gascon MP, Dayer P. 1991. In vitro forecasting of drugs which may interfere with the biotransformation of midazolam. Eur. J. Clin. Pharmacol. 41:573-78
166. Maurel P. 1996. The use of adult human hepatocytes in primary culture and other in vitro systems to investigate drug metabolism in man. Adv. Drug Deliv. Rev. 22:105-32
167. Pichard L, Gillet G, Fabre I, Dalet-Beluche I, Bonfils C, et al. 1990. Identification of the rabbit and human cytochromes P-450IIIA as the major enzymes involved in the N-demethylation of diltiazem. Drug Metab. Dispos. 18: 711-19
168. Ged C, Rouillon JM, Pichard L, Combalbert J, Bressot N, et al. 1989. The increase in urinary excretion of 6β-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. Br J. Clin. Pharmacol. 28:373-87
169. Brockmöller J, Roots I. 1994. Assessment of liver metabolic function: clinical implications. Clin. Pharmacokin. 27:216-48
170. Wilkinson GR. 1987. Clearance approaches in pharmacology. Pharmacol. Rev. 39:1-47
171. Bartkowski RR, Goldberg ME, Larijani GE, Boerner T. 1989. Inhibition of alfentanil metabolism by erythromycin. Clin. Pharmacol. Ther. 46:99-102
172. Kolars JC, Awni WM, Merion RM, Watkins PB. 1991. First-pass metabolism of cyclosporin by the gut. Lancet 338:1488-90
173. Paine MF, Shen DD, Kunze KL, Perkins JD, Marsh CL, et al. 1996. First-pass metabolism of midazolam by the human intestine. Clin. Pharmacol. Ther. 60:14-24
174. Gupta SK, Bakran A, Johnson RWG, Rowland M. 1988. Erythromycin enhances the absorption of cyclosporin. Br. J. Clin. Pharmac. 25:401-2
175. Floren LC, Bekersky I, Benet LZ, Mekki Q, Dressler D, et al. 1997. Tacrolimus oral bioavailability doubles with coadministration of ketoconazole. Clin. Pharmacol. Ther. 62:41-19
176. Herbert MF, Roberts JP, Prueksaritanont T, Benet LZ. 1992. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin. Pharmacol. Ther. 52:453-57
177. Fromm MF, Busse D, Kroemer HK, Eichelbaum M. 1996. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology 24:796-801
178. Holtbecker N, Fromm MF, Kroemer HK, Ohnhaus EE, Heidemann H. 1996. The nifedipine-rifampin interaction -evidence for induction of gut wall metabolism. Drug Metab. Dispos. 24:1121-23
179. Park GR, Manara AR, Dawling S. 1989. Extra-hepatic metabolism of midazolam. Br. J. Clin. Pharmacol. 27:634-37
180. Thummel KE, O'Shea D, Paine MF, Shen DD, Kunze KL, et al 1996. Oral first-pass elimination of midazolam involves both gastro-intestinal and hepatic CYP3A-mediated metabolism. Clin. Pharmacol. Ther. 59:491-502
181. Kupferschmidt HHT, Ha HR, Ziegler WH. Meier PJ. Krähenbühl S. 1995. Interaction between grapefruit juice and midazolam in humans. Clin. Pharmacol. Ther. 58:20-28
182. Varhe A, Olkkola KT, Neuvonen PJ. 1996. Effect of fluconazole dose on the extent of fluconazole-triazolam interaction. Br. J. Clin. Pharmacol. 42:465-70
183. Lundahl J, Regårdh CG, Edgar B, Johnsson G. 1995. Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur. J. Clin. Pharmacol. 49:61-67
184. Hippius M, Henschel L, Sigusch H, Tepper J, Brendel E, Hoffmann A. 1995. Pharmacokinetic interactions of nifedipine and quinidine. Pharmazie 50:613-16
185. Schellens JHM, Ghabrial H, van der Wart HHF, BakkerEN, Wilkinson GR, Breimer DD. 1991. Differential effects of quinidine on the disposition of nifedipine, sparteine, and mephenytoin in humans. Clin. Pharmacol. Ther. 50:520-28
186. Bowles SK, Reeves RA, Cardozo L, Edwards DJ. 1993. Evaluation of the pharmacokinetic and pharmacodynamic interaction between quinidine and nifedipine. J. Clin. Pharmacol. 33:727-31
187. Neuvonen PJ, Varhe A, Olkkola KT. 1996. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin. Pharmacol. Ther. 60:326-31
188. Schimke RT, Doyle D. 1970, Control of enzyme levels in animal tissues. Annu. Rev. Biochem. 39:929-76
189. Lee KH, Shin JG, Chong WS, Kim S, Lee JS, et al. 1993. Time course of the changes in prednisolone pharmacokinetics after co-administration or discontinuation of rifampin. Eur. J. Clin. Pharmacol. 45:287-89
190. Hellriegel ET, Bjornsson TD, Hauck WW. 1996. Interpatient variability in bioavailability is related to the extent of absorption: implications for bioavailability and bioequivalence studies. Clin. Pharmacol. Ther. 60:601-7
191. Honig PK, Wortham DC, Zamani K, Cantilena LR. 1994. Comparison of the effect of the macrolide antibiotics erythromycin, clarithromycin and azithromycin on terfenadine steady-state pharmacokinetics and electrocardiographic parameters. Drug Invest. 7:148-56
192. Honig PK, Wortham DC, Zamani K, Conner DP, Mullin JC, Cantilena LR. 1993. Terfenadine-ketoconazole interaction -pharmacokinetic and electrocardiographic consequences. JAMA 269:1513-18
193. Yee GC, Stanley DL, Pessa LJ, Dalla Costa T, Beltz SE, et al. 1995. Effect of grapefruit juice on blood cyclosporin concentration. Lancet 345:955-56
194. Bailey DG, Spence JD, Munoz C, Arnold JMO. 1991. Interaction of citrus juices with felodipine and nifedipine. Lancet 337:268-69
195. Edgar B, Bailey D, Bergstrand R, Johnsson G, Regårdh CG. 1992. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine - and its potential clinical relevance. Eur. J. Clin. Pharmacol. 42:313-17
196. Bailey DG, Bend JR, Arnold JMO, Tran LT, Spence JD. 1996 Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. Clin. Pharmacol. Ther. 60:25-33
197. Benton RE, Honig PK, Zamani K, Cantilena LR, Woosley RL. 1996. Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram. Clin. Pharmacol. Ther. 59:383-88
198. Rau SE, Bend JR, Arnold MO, Tran LT, Spence JD, Bailey DG. 1997. Grapefruit juice-terfenadine single-dose interaction: magnitude, mechanism, and relevance. Clin. Pharmacol. Ther. 61:401-9
199. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, et al. 1997. The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice. Eur. J. Clin. Pharmacol. 52:311-15
200. Olkkola KT, Backman JT, Neuvonen PJ. 1994. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin. Pharmacol. Ther. 55:481-85
201. Vanakoski J, Manila MJ, Seppälä. 1996. Grapefruit juice does not enhance the effects of midazolam and triazolam in man. Eur. J. Clin. Pharmacol. 50:501-8
202. Jones TE, Morris RG. 1996. Diltiazem does not always increase blood cyclosporin concentration. Br. J. Clin. Pharmacol. 42: 642-44
203. Watkins PB. 1994. Noninvasive tests of CYP3A enzymes. Pharmacogenetics 4:171-84
204. Park BK. 1981. Assessment of urinary 6β-hydroxycortisol as an in vivo index of mixed-function oxygenase activity. Br. J. Clin. Pharmacol. 12:97-102
205. Ohnhaus EE, Breckenridge AM, Park BK. 1989. Urinary excretion of 6β-hydroxycortisol and the time course measurement of enzyme induction in man. Eur. J. Clin. Pharmacol. 36:39-46
206. Waxman DJ, Attisano C, Guengerich FP, Lapenson DP. 1988. Human liver microsomal steroid metabolism: identification of the major microsomal steroid hormone 6β-hydroxylase cytochrome P-450 enzyme. Arch. Biochem. Biophys. 263:424-36
207. Horsmans Y, Desager JP, Harvengt C. 1992. Absence of CYP3A genetic polymorphism assessed by urinary excretion of 6β-hydroxycortisol in 102 healthy subjects on rifampicin. Pharmacol. Toxicol. 71:258-61
208. Roots I, Holbe R, Hövermann W, Nigam S, Heinemeyer G, Hildebrandt AG. 1979. Quantitative determination by HPLC of urinary 6β-hydroxycortisol, an indicator of enzyme induction by rifampicin and antiepileptic drugs. Eur. J. Clin. Pharmacol. 16:63-71
209. Saenger P, Forster E, Kream J. 1981. 6β-hydroxycortisol: a noninvasive indicator of enzyme induction. J. Endocrinol. Metab. 52:381-84
210. Saenger P. 1983. 6β-hydroxycortisol in random urine samples as an indicator of enzyme induction. Clin. Pharmacol. Ther. 34:818-21
211. Watkins PB, Turgeon DK, Saenger P, Lown KS, Kolars JC, et al. 1992. Comparison of urinary 6-β-cortisol and the erythromycin breath test as measures of hepatic P450IIIA (CYP3A) activity. Clin. Pharmacol. Ther. 52:265-73
212. Lown K, Kolars J, Turgeon K, Merion R, Wrighton SA, Watkins PB. 1992. The erythromycin breath test selectively measures P450IIIA in patients with severe liver disease. Clin. Pharmacol. Ther. 51:229-38
213. Hunt CM, Watkins PG, Saenger P, Stave GM, Barlascini N, et al. 1992. Heterogeneity of CYP3A isoforms metabolizing erythromycin and Cortisol. Clin. Pharmacol. Ther. 51:18-23
214. Kinirons MT, O'Shea D, Downing TE, Fitzswilliam AT, Joellenbeck L, et al. 1993. Absence of correlations among three putative in vivo probes of human cytochrome P4503A activity in young healthy men. Clin. Pharmacol. Ther. 54: 621-29
215. Lown KS, Thummel KE, Benedict PE, Shen DD, Turgeon DK, et al. 1995. The erythromycin breath test predicts the clearance of midazolam. Clin. Pharmacol. Ther. 57:16-24
216. Krivoruk Y, Kinirons MT, Wood AJJ, 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. Clin. Pharmacol. Ther. 56:608-14
217. Cheng C-L, Smith DE, Carver PL, Cox SR, Watkins PB, et al. 1997. Steady-state pharmacokinetics of delavirdine in HIV-positive patients: effect on erythromycin breath test. Clin. Pharmacol. Ther. 61:531-43
218. Jamis-Dow CA, Pearl ML, Watkins PB, Blake DS, Klecker RW, Collins JM. 1997. Predicting drug interactions in vivo from experiments in vitro: human studies with paclitaxel and ketoconazole. Am. J. Clin. Oncol. 20:592-99
219. Tateishi T, Graham SG, Krivoruk Y, Wood AJ. 1995. Omeprazole does not affect measured CYP3A4 activity using the erythromycin breath test. Br. J. Clin. Pharmacol. 40:411-12
220. Craig PI, Tapner M, Farrell GC, 1993. Interferon suppresses erythromycin metabolism in rats and human subjects. Hepatology 17:230-35
221. Thummel KE, Shen DD, Podoll TD, Kunze KL, Trager WF, et al. 1994. Use of midazolam as a human cytochrome P450 3A probe: I. In vitro-in vivo correlations in liver transplant patients. J. Pharmacol. Exp. Ther. 271:549-56
222. MacGilchrist AJ, Birnie GG, Cook A, Scobie G, Murray T, et al. 1986. Pharmacokinetics and pharmacodynamics of intravenous midazolam in patients with severe alcoholic cirrhosis. Gut 27: 190-95
223. Pentikäinen PJ, Välisalmi L, Himberg JJ, Crevoisier C. 1989. Pharmacokinetics of midazolam following intravenous and oral administration in patients with chronic liver disease and in healthy subjects. J. Clin. Pharmacol. 29:272-77
224. Backman JT, Olkkola KT, Neuvonen PJ. 1996. Rifampin drastically reduces plasma concentrations and effects of oral midazolam. Clin. Pharmacol. Ther. 59:7-13
225. Thummel KE, Kunze KL, Shen DD. 1997. Enzyme-catalyzed processes of first-pass hepatic and intestinal drug extraction. Adv. Drug Deliv. Rev. 27:99-127
226. Ahonen J, Olkkola KT, Neuvonen PJ. 1995. Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. Br. J. Clin. Pharmacol. 40: 270-72
227. Yeates RA, Laufen H, Zimmermann T. 1996. Interaction between midazolam and clarithromycin: comparison with azithromycin. Int. J. Clin. Pharmacol. Ther. 34:400-5
228. Backman JT, Arako K, Himberg JJ, Olkkola KT. 1994. A pharmacokinetic interaction between roxithromycin and midazolam. Eur. J. Clin. Pharmacol. 46: 551-55
229. Backman JT, Olkkola KT, Neuvonen PJ. 1995. Azithromycin does not increase plasma concentrations of oral midazolam. Int. J. Clin. Pharmacol. Ther. 33:356-59
230. Zimmermann T, Yeates RA, Laufen H, Scharpf E, Leitold M, et al. 1996. Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam. Arzneim.-Forsch./Drug Res. 46:213-17
231. Mattila MJ, Vanakoski J, Idänpään-Heikkilä JJ. 1994. Azithromycin does not alter the effects of oral midazolam on human performance. Eur. J. Clin. Pharmacol. 47:49-52
232. Watkins PG, Hamilton TA, Annesley TM, Ellis CN, Kolars JC, Voorhees JJ. 1990. The erythromycin breath test as a predictor of cyclosporine blood levels. Clin. Pharmacol. Ther. 48:120-29
233. Turgeon DK, Normolle DP, Leichtman AB, Annesley TM, Smith DE, Watkins PB. 1992. Erythromycin breath test predicts oral clearance of cyclosporine in kidney transplant recipients. Clin. Pharmacol. Ther. 52:471-78
234. Turgeon DK, Leichtman AB, Lown KS, Normolle DP, Deeb GM, Merion, et al. 1994. P4503A activity and cyclosporine dosing in kidney and heart transplant recipients. Clin. Pharmacol. Ther. 56:253-60
235. Stein CM, Kinirons MT, Pincus T, Wilkinson GR, Wood AJJ. 1996. Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A activity in patients with rheumatoid arthritis receiving cyclosporine. Clin. Pharmacol. Ther. 59:47-51
236. Yeates RA, Scharpf F, Laufen H, Zimmermann T. 1996. Screening for P4503A in man: studies with midazolam and nifedipine. J. Pharm. Pharmacol. 48:933-34
237. Mitra AK, Thummel KE, Kalhorn TF, Kharasch ED, Unadkat JD, Slattery JT. 1995. Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo. Clin. Pharmacol. Ther. 58:556-66
238. Gill HJ, Tingle MD, Park BK. 1995. N-Hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity. Br. J. Clin. Pharmacol. 40:531-38
239. Kinirons MT, O'Shea D, Groopman JD, Thummel KE, Wood AJJ, Wilkinson GR. 1994. Route of administration does not explain the lack of correlation between putative in vivo probes of cytochrome P4503A. Br. J. Clin. Pharmacol. 37:501P
240. Baciewicz AM, Baciewicz FA Jr. 1993. Ketoconazole and fluconazole drug interactions. Arch. Int. Med. 153:1970-76
241. Gillum JG, Israel DS, Polk RE. 1993. Pharmacokinetic drug interactions with antimicrobial agents. Clin. Pharmacokinet. 25:450-82
242. Periti P, Mazzei T, Mini E, Novelli A. 1992. Pharmacokinetic drug interactions of macrolides. Clin. Pharmacokinet. 23:106-31
243. von Rosensteil NA, Adam D. 1995. Macrolide antibacterials. Drug interactions of clinical significance. Drug Safety 13:105-22
244. Ketter TA, Flockhart DA, Post RM, Denicoff K, Pazzaglia PJ, et al. 1995. The emerging role of cytochrome P4503A in psychopharmacology. J. Clin. Psychopharmacol. 15:387-98
245. Harvey AT, Preskorn SH. 1996. Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors. Part II. J. Clin. Psychopharmacol. 16:345-55
246. Rosenthal T, Ezra D. 1995. Calcium antagonists. Drug interactions of clinical significance. Drug Safety 13:157-87
247. Grange JM, Winstanley PA, Davies PDO. 1994. Clinically significant drug interactions with antituberculosis agents. Drug Safety 11:242-51
248. Nation RL, Evans AM, Milne RW. 1990. Pharmacokinetic drug interactions with phenytoin (Part II). Clin. Pharmacokinet. 18:131-50
249. Ling K-HJ, Leeson GA, Burmaster SD, Hook RH, Reith MK, Cheng LK. 1995. Metabolism of terfenadine associated with CYP3A(4) activity in human hepatic microsomes. Drug Metab. Dispos. 23:631-36
250. Yun C-H, Okerholm RA, Guengerich FP. 1993. Oxidation of the antihistaminic drug terfenadine in human liver microsomes - role of cytochrome P-450 3A(4) in N-Dealkylation and C-hydroxylation. Drug Metab. Dispos. 21:403-9
251. Jurima-Romet M, Crawford K, Cyr T, Inaba T. 1994. Terfenadine metabolism in human liver - in vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab. Dispos. 22:849-57
252. Woosley RL. 1996. Cardiac actions of antihistamines. Annu. Rev. Pharmacol. Toxicol. 36:233-52
253. Woosley RL, Chen Y, Freiman JP, Gillis RA. 1993. Mechanism of the cardiotoxic actions of terfenadine. JAMA 269:1532-36
254. Kivistö KT, Neuvonen PJ, Klotz U. 1994. Inhibition of terfenadine metabolism -pharmacokinetic and pharmacodynamic consequences. Clin. Pharmacokinet. 27: 1-5
255. Botstein P. 1993. Is QT interval prolongation harmful? A regulatory perspective. Am. J. Cardiol. 72:50B-52B
256. Brannan MD, Affrime MB, Radwanski E, Cayen MN, Banfield C. 1995. Effects of various cytochrome P450 inhibitors on the metabolism of loratadine. Clin. Pharmacol. Ther. 57:193
257. First MR, Schroeder TJ, Alexander JW, Stephens GW, Weiskittel P, et al. 1991. Cyclosporine dose reduction by ketoconazole administration in renal transplant recipients. Transplantation 51:365-70
258. Butman SM, Wild JC, Nolan PE, Fagan TC, Finley PR, et al. 1991. Prospective study of the safety and financial benefit of ketoconazole as adjunctive therapy to cyclosporine after heart transplantation. J. Heart Lung Transplant. 10:351-58
259. First MR, Schroeder TJ, Michael A, Hariharan S, Weiskittel P, Alexander JW. 1993. Safety and efficacy of long-term cyclosporine-ketoconazole administration and preliminary results of a randomized trial. Transplant. Proc. 25:591-94
260. Patton PR, Brunson ME, Pfaff WW, Howard RJ, Peterson JC, et al. 1994. A preliminary report of diltiazem and ketoconazole - their cyclosporine-sparing effeet and impact on transplant outcome. Transplantation 57:889-92
261. Keogh A, Spratt P, McCosker C, Macdonald P, Mundy J, Kanna A. 1995. Ketoconazole to reduce the need for cyclosporine after cardiac transplantation. N. Engl. J. Med. 333:628-33
262. Sobh M, El-Agroudy A, Moustafa F, Harras F, El-Bedewy M, Ghoneim M. 1995. Coadministration of ketoconazole to cyclosporin-treated kidney transplant recipients: a prospective randomized study. Am. J. Nephrol. 15:493-99
263. Valantine H, Koegh A, McIntosh N, Hunt S, Oyer P, Schroeder J. 1992. Cost containment: coadministration of diltiazem with cyclosporine after heart transplantation. J. Heart Lung Transplant. 11:1-8
264. Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, et al. 1995. Clinical pharmacokinetics of tacrolimus. Clin. Pharmacokinet. 29:404-30
265. Varhe A, Olkkola KT, Neuvonen PJ. 1994. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin. Pharmacol. Ther. 56:601-7
266. Varhe A, Olkkola KT, Neuvonen PJ. 1996. Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism. Br. J. Clin. Pharmacol. 41:319-23
267. Phillips JP, Antal EJ, Smith RB. 1986. A pharmacokinetic drug interaction between erythromycin and triazolam. J. Clin. Psychopharmacol. 6:297-99
268. Greene DS, Dockens RC, Salazar DE, Barbhaiya RH. 1994. Coadministration of nefazodone (NEF) and benzodiazepines I: pharmacokinetic assessment. Clin. Pharmacol. Ther. 55:141
269. Yasui N, Otani K, Kaneko S, Ohkubo T, Osanai T, et al. 1996. A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3A4 in alprazolam metabolism. Clin. Pharmacol. Ther. 59:514-19
270. Lasher TA, Fleishaker JC, Steenwyk RC, Antal EJ. 1991. Pharmacokinetic pharmacodynamic evaluation of the combined administration of alprazolam and fluoxetine. Psychopharmacology 104:323-27
271. Greenblatt DJ, Preskorn SH, Cotreau MM, Horst WD, Harmatz JS. 1992. Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clin. Pharmacol. Ther. 52:479-86
272. Fleishaker JC, Hulst LK. 1994. A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur. J. Clin. Pharmacol. 46:35-39
273. Villikka K, Kivistö KT, Backman JT, Olkkola KT, Neuvonen PJ. 1997. Triazolam is ineffective in patients taking rifampin. Clin. Pharmacol. Ther. 61:8-14
274. Arana GW, Epstein S, Molloy M, Greenblatt DJ. 1988. Carbamazepine-induced reduction of plasma alprazolam concentrations: a clinical case report. J. Clin. Psychiatry 49:448-49
275. Lai AA, Levy RH, Cutler RE. 1978. Time-course of interaction between carbamazepine and clonazepam in normal man. Clin. Pharmacol. Ther. 24:316-23
276. Backman JT, Olkkola KT, Ojala M, Laaksovirta H, Neuvonen PJ. 1996. Concentrations and effects of oral midazolam are greatly reduced in patients treated with carbamazepine orphenytoin. Epilepsia 37:253-57
277. Barry M, Gibbons S, Back D, Mulcahy F. 1997. Protease inhibitors in patients with HIV disease - clinically important pharmacokinetic considerations. Clin. Pharmacokinet. 32:194-209
278. Lin JH. 1996. Human immunodeficiency virus protease inhibitors: from drug design to clinical studies. Adv. Drug Deliv. Rev. 27:215-33
279. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJJ, et al. 1997. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. 101:289-94