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

To determine in humans the relative roles of intestinal and hepatic metabolism in the oral first‐pass elimination of a CYP3A substrate using midazolam as a model compound.

[1]  U Klotz,et al.  Midazolam kinetics , 1981, Clinical pharmacology and therapeutics.

[2]  J. Kolars,et al.  Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. , 1992, The Journal of clinical investigation.

[3]  Meindert Danhof,et al.  Pharmacokinetic‐pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite α‐hydroxymidazolam in healthy volunteers , 1992, Clinical pharmacology and therapeutics.

[4]  R. Rahmani,et al.  Characterization of midazolam metabolism using human hepatic microsomal fractions and hepatocytes in suspension obtained by perfusing whole human livers. , 1988, Biochemical pharmacology.

[5]  P. Heizmann,et al.  Excretion and metabolism of 14C-midazolam in humans following oral dosing. , 1981, Arzneimittel-Forschung.

[6]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[7]  D. Wortham,et al.  Terfenadine-ketoconazole interaction. Pharmacokinetic and electrocardiographic consequences. , 1993, JAMA.

[8]  J. Derancourt,et al.  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. , 1989, Drug metabolism and disposition: the biological fate of chemicals.

[9]  P. Neuvonen,et al.  Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. , 1995, Clinical pharmacology and therapeutics.

[10]  U. Klotz,et al.  Physiologie and temporal variation in hepatic elimination of midazolam , 1982, Clinical pharmacology and therapeutics.

[11]  D. Greenblatt,et al.  Norcocaine and N-hydroxynorcocaine formation in human liver microsomes: role of cytochrome P-450 3A4. , 1993, Pharmacology.

[12]  S. Pond,et al.  First-Pass Elimination Basic Concepts and Clinical Consequences , 1984, Clinical pharmacokinetics.

[13]  J. Kolars,et al.  CYP3A gene expression in human gut epithelium. , 1994, Pharmacogenetics.

[14]  F. Guengerich,et al.  Oxidation of the antihistaminic drug terfenadine in human liver microsomes. Role of cytochrome P-450 3A(4) in N-dealkylation and C-hydroxylation. , 1993, Drug metabolism and disposition: the biological fate of chemicals.

[15]  J W Dundee,et al.  Midazolam. A review of its pharmacological properties and therapeutic use. , 1984, Drugs.

[16]  R. Minchin,et al.  Presystemic elimination of drugs: theoretical considerations for quantifying the relative contribution of gut and liver. , 1982, Journal of pharmaceutical sciences.

[17]  T. Kronbach,et al.  Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. , 1989, Molecular pharmacology.

[18]  L. Benet,et al.  Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction , 1992, Clinical pharmacology and therapeutics.

[19]  W. Trager,et al.  Use of midazolam as a human cytochrome P450 3A probe: I. In vitro-in vivo correlations in liver transplant patients. , 1994, The Journal of pharmacology and experimental therapeutics.

[20]  E. Kharasch,et al.  Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1. , 1993, Drug metabolism and disposition: the biological fate of chemicals.

[21]  S D Hall,et al.  Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. , 1994, Biochemical pharmacology.

[22]  P. Watkins.  Noninvasive tests of CYP3A enzymes. , 1994, Pharmacogenetics.

[23]  P. Watkins,et al.  Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. , 1987, The Journal of clinical investigation.

[24]  U. Meyer,et al.  Lidocaine metabolism in human liver microsomes by cytochrome P450IIIA4 , 1989, Clinical pharmacology and therapeutics.

[25]  J. Kolars,et al.  Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test. , 1994, Drug metabolism and disposition: the biological fate of chemicals.

[26]  M. Relling,et al.  O-demethylation of epipodophyllotoxins is catalyzed by human cytochrome P450 3A4. , 1994, Molecular pharmacology.

[27]  A. Hiller,et al.  A potentially hazardous interaction between erythromycin and midazolam. , 1993, Clinical pharmacology and therapeutics.

[28]  J. Kolars,et al.  First-pass metabolism of cyclosporin by the gut , 1991, The Lancet.

[29]  P. Beaune,et al.  Cytochrome P 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues. , 1990, The Journal of pharmacology and experimental therapeutics.

[30]  G R Wilkinson,et al.  Clearance approaches in pharmacology. , 1987, Pharmacological reviews.

[31]  D. Waxman,et al.  Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. , 1986, The Journal of biological chemistry.

[32]  W. Trager,et al.  Use of midazolam as a human cytochrome P450 3A probe: II. Characterization of inter- and intraindividual hepatic CYP3A variability after liver transplantation. , 1994, The Journal of pharmacology and experimental therapeutics.

[33]  H. Sewell,et al.  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. , 1988, British journal of clinical pharmacology.