Midazolam and triazolam biotransformation in mouse and human liver microsomes: Relative contribution of CYP3a and CYP2C isoforms

Journal of Pharmacology and Experimental Therapeutics

Volumn 292, Issue 2, 2000, Pages 618-628

  Perloff, Michael D ^a   Von Moltke, Lisa L ^a,b   Court, Michael H ^a   Kotegawa, Tsutomu ^a   Shader, Richard I ^a,b   Greenblatt, David J ^a,b  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b TUFTS MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 ISOENZYME; KETOCONAZOLE; MIDAZOLAM; TRIAZOLAM;

ARTICLE; CONTROLLED STUDY; DRUG CLEARANCE; DRUG HYDROXYLATION; DRUG INHIBITION; DRUG METABOLISM; DRUG POTENCY; DRUG TRANSFORMATION; ENZYME SPECIFICITY; HUMAN; HUMAN TISSUE; LIVER MICROSOME; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; ANTIBODIES; ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; BLOTTING, WESTERN; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; IMMUNOCHEMISTRY; INHIBITORY CONCENTRATION 50; KETOCONAZOLE; MICE; MICROSOMES, LIVER; MIDAZOLAM; MIXED FUNCTION OXYGENASES; OXIDOREDUCTASES, N-DEMETHYLATING; PROTEIN ISOFORMS; SPECIES SPECIFICITY; STEROID 16-ALPHA-HYDROXYLASE; STEROID HYDROXYLASES; TRIAZOLAM;

EID: 0033979574     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (40)

1. Abel SM, Back DJ, Maggs JL and Park BK (1993) Cortisol metabolism in vitro: II. Species difference. J Steroid Biochem Mol Biol 45:445-453.
2. Benet L, Kroetz D and Sheiner L (1996) Pharmacokinetics: The dynamics of drug absorption, distribution, and elimination, in Goodman and Gilman's The Pharmacological Basis of Therapeutics (Hardman J, Limbird L, Molinoff P, Ruddon R and Gilman A eds) pp 3-28, McGraw-Hill, New York.
3. Chauret N, Gauthier A, Martin J and Nicoll-Griffith DA (1997) In vitro comparison of cytochrome P450-mediated metabolic activities in human, dog, cat, and horse. Drug Metab Dispos 25:1130-1136.
4. Court MH, von Moltke LL, Shader RI and Greenblatt DJ (1997) Biotransformation of chlorzoxazone by hepatic microsomes from humans and ten other mammalian species. Biopharm Drug Dispos 18:213-226.
5. Diliberto JJ, Burgin D and Birnbaum LS (1997) Role of CYP1A2 in hepatic sequestration of dioxin: Studies using CYP1A2 knock-out mice. Biochem Biophys Res Commun 236:431-433.
6. Eagling VA, Tjia JF and Back DJ (1998) Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br J Clin Pharmacol 45:107-114.
7. Echizen H, Mochizuki K, Tani M and Ishizaki T (1994) Interspecies differences in enantioselective mono-N-dealkylation of disopyramide by human and mouse liver microsomes. J Pharmacol Exp Ther 268:1518-1525.
8. Fahey JM, Pritchard GA, von Moltke LL, Pratt JS, Grassi JM, Shader RI and Greenblatt DJ (1998) Effects of ketoconazole on triazolam pharmacokinetics, pharmacodynamics and benzodiazepine receptor binding in mice. J Pharmacol Exp Ther 285:271-276.
9. Ghosal A, Satoh H, Thomas PE, Bush E and Moore D (1996) Inhibition and kinetics of cytochrome P4503A activity in microsomes from rat, human, and cDNA-expressed human cytochrome P450. Drug Metab Dispos 24:940-947.
10. Gorski JC, Hall SD, Jones DR, VandenBranden M and Wrighton SA (1994) Regioselective biotransformation of midazolam by members of the human cytochrome P4503A (CYP3A) subfamily. Biochem Pharmacol 47:1643-1653.
11. Guengerich FP (1997) Comparisons of catalytic selectivity of cytochrome P450 sub-family enzymes from different species. Chem Biol Interact 106:161-182.
12. Guo Z, Raeissi S, White RB and Stevens JC (1997) Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes. Drug Metab Dispos 23:390-393.
13. 14C-midazolam in humans following oral dosing. Arzneim Forsch 31:2220-2223.
14. Higashikawa F, Murakami T. Kaneda T, Kato A and Takano M (1999) Dose-dependent intestinal and hepatic first-pass metabolism of midazolam, a cytochrome P450 3A substrate with differently modulated enzyme activity in rats. J Pharm Pharmacol 51:67-72.
15. Kronbach T, Mathys D, Umeno M, Gonzalez FJ and Meyer UA (1989) Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol Pharmacol 36:89-96.
16. Laurijssens BE and Greenblatt DJ (1996) Pharmacokinetic-pharmacodynaraic relationships for benzodiazepines. Clin Pharmacokinet 30:52-76.
17. Maurel P (1996) The CYP3A family. In Cytochromes P450 (Ionnides C ed) pp 241-270, CRC Press, Boca Raton, FL.
18. Nebert DW and Duffy JJ (1997) How knockout mouse lines will be used to study the role of drug-metabolizing enzymes and their receptors during reproduction and development, and in environmental toxicity, cancer, and oxidative stress. Biochem Pharmacol 53:249-254.
19. Newton DJ. Wang RW and Lu AY (1995) Cytochrome P450 inhibitors. Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23:154-158.
20. Ono S, Hatanaka T, Hotta H, Satoh T, Gonzalez FJ and Tsutsui M (1996) Specificity of substrate and inhibitor probes for cytochrome P450s: Evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica 26:681-693.
21. Perloff MD, von Moltke LL, Cotreau MM and Greenblatt DJ (1999) Unchanged cytochrome P450 3A (CYP3A) expression and metabolism of midazolam, triazolam, and dexamethasone in mdr(-/-) mouse liver microsomes. Biochem Pharmacol 57:1227-1232.
22. Schmider J, Greenblatt DJ, von Moltke LL, Harmatz JS, Duan SX, Karsov D and Shader RI (1996) Characterization of six in vitro reactions mediated by human cytochrome P450: Application to the testing of cytochrome P450-directed antibodies. Pharmacology 52:125-134.
23. Segel IH (1975) Enzyme Kinetics. Wiley, New York.
24. Sharer JE, Shipley LA, Vandenbranden MR, Binkley SN and Wrighton SA (1995) Comparisons of phase I and phase II in vitro hepatic enzyme activities of human, dog, rhesus monkey, and cynomolgus monkey. Drug Metab Dispos 23:1231-1241.
25. Shimada T, Yamazaki H, Mimura M, Inui Y and 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 270:414-423.
26. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ and Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76-85.
27. Thummel KE, Shen DD, Podoll TD, Kunze KL, Trager WF, Hartwell PS, Raisys VA, Marsh CL, McVicar JP, Barr DM, Perkins JD and Carithers RL Jr (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 271:549-556.
28. Tomlinson ES, Maggs JL, Park BK and Back DJ (1997) Dexamethasone metabolism in vitro: Species differences. J Steroid Binchem Mol Biol 62:345-352.
29. Valentine JL, Lee SS, Seaton MJ, Asgharian B, Farris G, Corton JC, Gonzalez FJ and Medinsky MA (1996) Reduction of benzene metabolism and toxicity in mice that lack CYP2E1 expression. Toxicol Appl Pharmacol 141:205-213.
30. Venkatakrishnan K, Greenblatt DJ, von Moltke LL and Shader RI (1998a) Alprazolam is another substrate for human cytochrome P450-3A isoforms. J Clin Psychopharmacol 18:256.
31. Venkatakrishnan K, von Moltke LL, Duan SX, Fleishaker JC, Shader RI and Greenblatt DJ (1998b) Kinetic characterization and identification of the enzymes responsible for the hepatic biotransformation of adinazolam and N-desmethyladinazolam in man. J Pharm Pharmacol 50:265-274.
32. von Moltke LL, Greenblatt DJ, Grassi JM, Granda BW, Venkatakrishnan K, Schmider J, Harmatz JS and Shader RI (1998) Multiple human cytochromes contribute to biotransformation of dextromethorphan in-vitro: Role of CYP2C9, CYP2C19, CYP2D6, and CYP3A. J Pharm Pharmacol 50:997-1004.
33. von Moltke LL, Greenblatt DJ, Harmatz JS, Duan SX, Harrel LM, Cotreau-Bibbo MM, Pritchard GA, Wright CE and Shader RI (1996a) 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 276:370-379.
34. von Moltke LL, Greenblatt DJ, Harmatz JS and Shader RI (1993) Alprazolam metabolism in vitro: Studies of human, monkey, mouse, and rat liver microsomes. Pharmacology 47:268-276.
35. von Moltke LL, Greenblatt DJ, Schmider J, Duan SX, Wright CE, Harmatz JS and Shader RI (1996b) Midazolam hydroxylation by human liver microsomes in vitro: Inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents. J Clin Pharmacol 36:783-791.
36. Wandel C, Bocker RH, Bohrer H, deVries JX, Hofmann W, Walter K, Kleingeist B, Neff S, Ding R, Walter-Sack I and Martin E (1998) Relationship between hepatic cytochrome P450 3A content and activity and the disposition of midazolam administered orally. Drug Metab Dispos 26:110-114.
37. Warrington JS, Poku JW, von Moltke LL, Shader RI, Harmatz JS and Greenblatt DJ (2000) The effects of age on in vitro midazolam biotransformation in male CD-1 mouse liver microsomes. J Pharmacol Exp Ther, in press.
38. Whalen RD, Tata PN, Burckart GJ and Venkataramanan R (1999) Species differences in the hepatic and intestinal metabolism of cyclosporine. Xenobiotica 29:3-9.
39. Yanagimoto T, Itoh S, Muller-Enoch D and Kamataki T (1992) Mouse liver cytochrome P-450 (P-450IIIAM1): Its cDNA cloning and inducibility by dexamethasone. Biochim Biophys Acta 1130:329-332.
40. Zhao XJ and Ishizaki T (1997) The in vitro hepatic metabolism of quinine in mice, rats and dogs: Comparison with human liver microsomes. J Pharmacol Exp Ther 283:1168-1176.