Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism

Clinical Pharmacology and Therapeutics

Volumn 59, Issue 5, 1996, Pages 491-502

  Thummel, Kenneth E ^b   O'Shea, Diarmuid ^b   Paine, Mary F ^b   Shen, Danny D ^b   Kunze, Kent L ^b   Perkins, James D ^b   Wilkinson, Grant R ^a  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 ISOENZYME; DRUG METABOLITE; MIDAZOLAM;

ADULT; ARTICLE; BIOAVAILABILITY; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG DISPOSITION; DRUG METABOLISM; DRUG PROTEIN BINDING; FEMALE; GENDER; HUMAN; HUMAN EXPERIMENT; HUMAN TISSUE; INTESTINE; LIVER MICROSOME METABOLISM; MALE; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; PHARMACOKINETICS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; VOLUNTEER;

ADMINISTRATION, ORAL; ADULT; BIOLOGICAL AVAILABILITY; BLOOD PROTEINS; CYTOCHROME P-450 CYP2E1; CYTOCHROME P-450 ENZYME SYSTEM; EPITHELIUM; FEMALE; GABA MODULATORS; HUMANS; INJECTIONS, INTRAVENOUS; INTESTINE, SMALL; MALE; MICROSOMES; MICROSOMES, LIVER; MIDAZOLAM; MIXED FUNCTION OXYGENASES; PROTEIN BINDING; REGRESSION ANALYSIS; SEX FACTORS;

EID: 0030015297     PISSN: 00099236     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0009-9236(96)90177-0     Document Type: Article

References (38)

1. deWaziers I, Cugnenc PH, Yang CS, Leroux JP, Beaune PH. Cytochrome P450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues. J Pharmacol Exp Ther 1990;253:387-94.
2. Guengerich FP, Martin MV, Beaune PH, Kremers P, Wolff T, Waxman DJ. 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 1986;261:5051-60.
3. Kronbach T, Mathys D, Umeno M, Gonzalez FJ, Meyer UA. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol Pharmacol 1989;36:89-96.
4. Relling MV, Nemec J, Schuetz EG, Schuetz JD, Gonzalez FJ, Korzekwa KR. O-Demethylation of epipodophyllotoxins in catalyzed by human cytochrome P450 3A4. Mol Pharmacol 1994;45:352-8.
5. Bargetzi MJ, Aoyama T, Gonzalez FJ, Meyer UA. Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4. Clin Pharmacol Ther 1989;46: 521-7.
6. Yun CH, Okerholm RA, Guengerich FP. 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 1993;21:403-9.
7. LeDuc BW, Sinclair PR, Shuster L, Sinclair JF, Evans JE, Greenblatt DJ. Norcocaine and N-hydroxynorcocaine formation in human liver microsomes: roles of cytochrome P-4503A4. Pharmacology 1993;46:294-300.
8. Combalbert J, Fabre I, Fabre G, et al. 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 1989; 17:197-207.
9. Benet LZ, Øie S, Schwartz JB. Design and optimization of dosage regimens; pharmacokinetic data. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, eds. Goodman and Gilman's The Pharmacologic Basis of Therapeutics. New York: Pergamon Press, 1995:1707-92.
10. Kolars JC, Awni WM, Merion RM, Watkins PB. First-pass metabolism of cyclosporin by the gut. Lancet 1991;338:1488-90.
11. Kolars JC, Schmeidlin-Ren P, Scheutz JD, Fang C, Watkins PB. Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992;90:1871-8.
12. Hebert MF, Roberts JP, Prueksaritanont T, Benet LZ. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin Pharmacol Ther 1992;52:453-7.
13. Fabre G, Rahmani R, Placidi M, et al. Characterization of midazolam metabolism using human hepatic microsomal fractions and hepatocytes in suspension obtained by perfusing whole human livers. Biochem Pharmacol 1988;37:4389-97.
14. Gorski JC, Hall SD, Jones DR, VandenBranden M, Wrighton SA. Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol 1994;47:1643-53.
15. Dundee JW, Halliday NJ, Harper KW, Brogden RN. Midazolam: a review of its pharmacologic properties and therapeutic use. Drugs 1984;28:519-43.
16. Thummel KE, Shen DD, Podoll TD, et al. Use of midazolam as a human cytochrome P450 3A probe; I: in vitro - in vivo correlations in liver transplant patients. J Pharmacol Exp Ther 1994;271:549-56.
17. 2-valproic acid to rat plasma proteins. Pharm Res 1990;7:461-7.
18. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: Marcel Dekker, 1982.
19. Wilkinson GR. Clearance approaches in pharmacology. Pharmacol Rev 1987;39:1-47.
20. Pirttiaho HI, Sotaniemi EA, Pelkonen RO, Pitkänen U. Hepatic blood flow and drug metabolism in patients on enzyme-inducing anticonvulsants. Eur J Clin Pharmacol 1982;22:441-5.
21. Smith MT, Eadie MJ, O'Rourke Brophy T. The pharmacokinetics of midazolam in man. Eur J Clin Pharmacol 1981;19:271-8.
22. Pond SM, Tozer TN. First-pass elimination - basic concepts and clinical consequences. Clin Pharmacokinet 1984;9:1-25.
23. Thummel KE, Kharasch ED, Podoll T, Kunze K. Human liver microsomal enflurane defluorination catalyzed by cytochrome P450 2E1. Drug Metab Dispos 1993;21:350-7.
24. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.
25. Allonen H, Ziegler G, Klotz U. Midazolam kinetics. Clin Pharmacol Ther 1981;30:653-61.
26. Klotz U, Ziegler G. Physiologic and temporal variation in hepatic elimination of midazolam. Clin Pharmacol Ther 1982;32:107-12.
27. Mandema JW, Tuk B, van Steveninck AL, Breimer DD, Cohen AF, Danhof M. Pharmacokineticpharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite α-hydroxymidazolam in healthy volunteers. Clin Pharmacol Ther 1992;51:715-28.
28. Murray GI, Barnes TS, Sewell HF, Ewen SWB, Melvin WT, Burke MD. The immunocytochemical localisation and distribution of cytochrome P-450 in normal human hepatic and extrahepatic tissues with a monoclonal antibody to human cytochrome P-450. Br J Clin Pharmacol 1988;25:465-75.
29. 14C-midazolam in humans following oral dosing. Arzneimittelforschung 1981;31:2220-3.
30. Thummel KE, Shen DD, Podoll T, et al. Use of midazolam as a human cytochrome P450 3A probe; II: characterization of inter- and intraindividual hepatic P450 3A variability after liver transplantation. J Pharmacol Exp Ther 1994;271:557-66.
31. Kolars JC, Lown KS, Schmiedlin-Ren P, et al. CYP3A gene expression in human gut epithelium. Pharmacogenetics 1994;4:247-59.
32. Watkins PB, Wrighton SA, Schuetz EG, Molowa DT, Guzelian PS. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J Clin Invest 1987;80:1029-36.
33. Lown KS, Kolars JC, Thummel KE, et al. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: lack of prediction by the erythromycin breath test. Drug Metab Dispos 1994;22:947-55.
34. Minchin RF, Ilett KF. Presystemic elimination of drugs: theoretical considerations for quantifying the relative contribution of gut and liver. J Pharm Sci 1981;71:458-60.
35. Watkins PB. Non-invasive tests of CYP3A enzymes. Pharmacogenetics 1994;4:171-84.
36. Honig PK, Wortham DC, Zamani K, Conner DP, Mullin JC, Cantilena LR. Terfenadine-ketoconazole interaction: pharmacokinetic and electrocardiographic consequences. JAMA 1993;269:1513-8.
37. Olkkola KT, Backman JT, Neuvonen PJ. Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994;55:481-5.
38. Olkkola KT, Aranko K, Luurila H, et al. A potentially hazardous interaction between erythromycin and midazolam. Clin Pharmacol Ther 1993;53:298-305.