Drug interaction of efavirenz and midazolam: Efavirenz activates the CYP3A-mediated midazolam 1′-hydroxylation in vitro

Drug Metabolism and Disposition

Volumn 40, Issue 6, 2012, Pages 1178-1182

  Keubler, Anja ^a   Weiss, Johanna ^a   Haefeli, Walter E ^a   Mikus, Gerd ^a   Burhenne, Jürgen ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA HYDROXYMIDAZOLAM; CYTOCHROME B5; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; EFAVIRENZ; KETOCONAZOLE; MIDAZOLAM;

ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG HYDROXYLATION; DRUG METABOLISM; DRUG POTENTIATION; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER MICROSOME; MICHAELIS MENTEN KINETICS; PRIORITY JOURNAL;

BENZOXAZINES; CYTOCHROME P-450 CYP3A; DRUG INTERACTIONS; ENZYME ACTIVATION; HUMANS; HYDROXYLATION; MICROSOMES, LIVER; MIDAZOLAM;

EID: 84862092135     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.043844     Document Type: Article

References (42)

1. Adkins JC and Noble S (1998) Efavirenz. Drugs 56:1055-1064; discussion 1065-1066.
2. Atkins WM (2005) Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions. Annu Rev Pharmacol Toxicol 45:291-310.
3. Atkins WM (2006) Current views on the fundamental mechanisms of cytochrome P450 allosterism. Expert Opin Drug Metab Toxicol 2:573-579.
4. Bayer J, Heinrich T, Burhenne J, Haefeli WE, and Mikus G (2009) Potential induction of CYP3A4 after a single-dose of efavirenz using midazolam pharmacokinetics as a marker. Basic Clin Pharmacol Toxicol 104:515.
5. Christensen H, Hestad AL, Molden E, and Mathiesen L (2011) CYP3A5-mediated metabolism of midazolam in recombinant systems is highly sensitive to NADPH-cytochrome P450 reductase activity. Xenobiotica 41:1-5.
6. Egnell AC, Houston B, and Boyer S (2003) In vivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine. J Pharmacol Exp Ther 305:1251-1262. (Pubitemid 36618005)
7. Galetin A, Clarke SE, and Houston JB (2002) Quinidine and haloperidol as modifiers of CYP3A4 activity: multisite kinetic model approach. Drug Metab Dispos 30:1512-1522. (Pubitemid 35397061)
8. Gibbs MA, Thummel KE, Shen DD, and Kunze KL (1999) Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of Ki values and impact of CYP3A5 expression. Drug Metab Dispos 27:180-187. (Pubitemid 29072069)
9. Gorski JC, Hall SD, Jones DR, VandenBranden M, and Wrighton SA (1994) Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol 47:1643-1653. (Pubitemid 24167278)
10. Guengerich FP (2006) Cytochrome P450s and other enzymes in drug metabolism and toxicity. AAPS J 8:E101-E111.
11. Hafner V, Jäger M, Matthée AK, Ding R, Burhenne J, Haefeli WE, and Mikus G (2010) Effect of simultaneous induction and inhibition of CYP3A by St John's Wort and ritonavir on CYP3A activity. Clin Pharmacol Ther 87:191-196.
12. Hariparsad N, Nallani SC, Sane RS, Buckley DJ, Buckley AR, and Desai PB (2004) Induction of CYP3A4 by efavirenz in primary human hepatocytes: comparison with rifampin and phenobarbital. J Clin Pharmacol 44:1273-1281. (Pubitemid 39391486)
13. Henshall J, Galetin A, Harrison A, and Houston JB (2008) Comparative analysis of CYP3A heteroactivation by steroid hormones and flavonoids in different in vitro systems and potential in vivo implications. Drug Metab Dispos 36:1332-1340. (Pubitemid 351929318)
14. Hosea NA, Miller GP, and Guengerich FP (2000) Elucidation of distinct ligand binding sites for cytochrome P450 3A4. Biochemistry 39:5929-5939. (Pubitemid 30327066)
15. Hummel MA, Gannett PM, Aguilar JS, and Tracy TS (2004) Effector-mediated alteration of substrate orientation in cytochrome P450 2C9. Biochemistry 43:7207-7214. (Pubitemid 38720538)
16. Hutzler JM and Tracy TS (2002) Atypical kinetic profiles in drug metabolism reactions. Drug Metab Dispos 30:355-362. (Pubitemid 34263817)
17. Hutzler JM, Wienkers LC, Wahlstrom JL, Carlson TJ, and Tracy TS (2003) Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations. Arch Biochem Biophys 410:16-24. (Pubitemid 36268792)
18. Kapelyukh Y, Paine MJ, Maréchal JD, Sutcliffe MJ, Wolf CR, and Roberts GC (2008) Multiple substrate binding by cytochrome P450 3A4: estimation of the number of bound substrate molecules. Drug Metab Dispos 36:2136-2144.
19. Khan KK, He YQ, Domanski TL, and Halpert JR (2002) Midazolam oxidation by cytochrome P450 3A4 and active-site mutants: an evaluation of multiple binding sites and of the metabolic pathway that leads to enzyme inactivation. Mol Pharmacol 61:495-506. (Pubitemid 34171915)
20. 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. (Pubitemid 19191264)
21. Lin JH and Lu AY (1998) Inhibition and induction of cytochrome P450 and the clinical implications. Clin Pharmacokinet 35:361-390. (Pubitemid 28520008)
22. Mäenpää J, Hall SD, Ring BJ, Strom SC, and Wrighton SA (1998) Human cytochrome P450 3A (CYP3A) mediated midazolam metabolism: the effect of assay conditions and regioselective stimulation by alpha-naphthoflavone, terfenadine and testosterone. Pharmacogenetics 8:137-155. (Pubitemid 28227322)
23. Mannu J, Jenardhanan P, and Mathur PP (2011) A computational study of CYP3A4 mediated drug interaction profiles for anti-HIV drugs. J Mol Model 17:1847-1854.
24. Martínez C, Gervasini G, Agúndez JA, Carrillo JA, Ramos SI, García-Gamito FJ, Gallardo L, and Benítez J (2000) Modulation of midazolam 1-hydroxylation activity in vitro by neurotransmitters and precursors. Eur J Clin Pharmacol 56:145-151.
25. Mouly S, Lown KS, Kornhauser D, Joseph JL, Fiske WD, Benedek IH, and Watkins PB (2002) Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in humans. Clin Pharmacol Ther 72:1-9. (Pubitemid 34833182)
26. Mutlib AE, Chen H, Nemeth GA, Markwalder JA, Seitz SP, Gan LS, and Christ DD (1999) Identification and characterization of efavirenz metabolites by liquid chromatography/mass spectrometry and high field NMR: species differences in the metabolism of efavirenz. Drug Metab Dispos 27:1319-1333.
27. Ngui JS, Chen Q, Shou M, Wang RW, Stearns RA, Baillie TA, and Tang W (2001) In vitro stimulation of warfarin metabolism by quinidine: increases in the formation of 4′- and 10-hydroxywarfarin. Drug Metab Dispos 29:877-886. (Pubitemid 32488645)
28. Okada Y, Murayama N, Yanagida C, Shimizu M, Guengerich FP, and Yamazaki H (2009) Drug interactions of thalidomide with midazolam and cyclosporine A: heterotropic cooperativity of human cytochrome P450 3A5. Drug Metab Dispos 37:18-23.
29. Schenkman JB and Jansson I (2003) The many roles of cytochrome b5. Pharmacol Ther 97:139-152.
30. Shou M, Grogan J, Mancewicz JA, Krausz KW, Gonzalez FJ, Gelboin HV, and Korzekwa KR (1994) Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 33:6450-6455. (Pubitemid 24189354)
31. Smith PF, DiCenzo R, and Morse GD (2001) Clinical pharmacokinetics of non-nucleoside reverse transcriptase inhibitors. Clin Pharmacokinet 40:893-905. (Pubitemid 34066687)
32. Sugiyama M, Fujita K, Murayama N, Akiyama Y, Yamazaki H, and Sasaki Y (2011) Sorafenib and sunitinib, two anticancer drugs, inhibit CYP3A4-mediated and activate CY3A5-mediated midazolam 1′-hydroxylation. Drug Metab Dispos 39:757-762.
33. Tang W, Stearns RA, Kwei GY, Iliff SA, Miller RR, Egan MA, Yu NX, Dean DC, Kumar S, Shou M, et al. (1999) Interaction of diclofenac and quinidine in monkeys: stimulation of diclofenac metabolism. J Pharmacol Exp Ther 291:1068-1074.
34. Thummel KE, Shen DD, Podoll TD, Kunze KL, Trager WF, Hartwell PS, Raisys VA, Marsh CL, McVicar JP, and Barr DM (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. (Pubitemid 24333173)
35. Thummel KE and Wilkinson GR (1998) In vitro and in vivo drug interactions involving human CYP3A. Annu Rev Pharmacol Toxicol 38:389-430. (Pubitemid 28231501)
36. von Moltke LL, Greenblatt DJ, Granda BW, Giancarlo GM, Duan SX, Daily JP, Harmatz JS, and Shader RI (2001) Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. J Clin Pharmacol 41:85-91.
37. Ward BA, Gorski JC, Jones DR, Hall SD, Flockhart DA, and Desta Z (2003) The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther 306:287-300. (Pubitemid 36734384)
38. Weiss J, Herzog M, König S, Storch CH, Ketabi-Kiyanvash N, and Haefeli WE (2009) Induction of multiple drug transporters by efavirenz. J Pharmacol Sci 109:242-250.
39. Woods CM, Fernandez C, Kunze KL, and Atkins WM (2011) Allosteric activation of cytochrome P450 3A4 by α-naphthoflavone: branch point regulation revealed by isotope dilution analysis. Biochemistry 50:10041-10051.
40. Yamaori S, Yamazaki H, Suzuki A, Yamada A, Tani H, Kamidate T, Fujita K, and Kamataki T (2003) Effects of cytochrome b(5) on drug oxidation activities of human cytochrome P450 (CYP) 3As: similarity of CYP3A5 with CYP3A4 but not CYP3A7. Biochem Pharmacol 66:2333-2340. (Pubitemid 37456741)
41. Yang J, Atkins WM, Isoherranen N, Paine MF, and Thummel KE (2012) Evidence of CYP3A allosterism in vivo: analysis of interaction between fluconazole and midazolam. Clin Pharmacol Ther 91:442-449.
42. Zhou D, Andersson TB, and Grimm SW (2011) In vitro evaluation of potential drug-drug interactions with ticagrelor: cytochrome P450 reaction phenotyping, inhibition, induction, and differential kinetics. Drug Metab Dispos 39:703-710.