title: Contribution of cytochrome P450 3A pathway to bromocriptine metabolism and effects of ferrous iron and hypoxia-re-oxygenation on its elimination in the perfused rat liver.
abstract: The contribution of the cytochrome P450 3A pathway to bromocriptine metabolism, and the effects of ferrous iron and hypoxia-re-oxygenation on its elimination, were evaluated with the perfused rat liver. Outflow profiles of bromocriptine after bolus administration were estimated by moment analysis and dispersion model analysis. Kinetic parameters were not significantly changed by troleandomycin, a P450 3A inhibitor. The inhibition of bromocriptine metabolism by troleandomycin was 5.7 +/- 2.4%. These findings indicate that cytochrome P450 3A does not play an important role in bromocriptine elimination with the perfused rat liver. Elimination rate constant (ka) values were significantly increased by ferrous iron perfusion or hypoxia-re-oxygenation. Free-radical generation can, therefore, affect bromocriptine elimination. Our observations suggest that bromocriptine might be eliminated by scavenging of free radicals in the liver.
authors.affiliation: Department of Legal Medicine, Kyoto University Faculty of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsubayashi
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.forename: Y
authors.initials: Y
authors.lastname: Fukui
mesh_terms: D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D001825:Body Fluid Compartments; D001971:Bromocriptine / Q000378:metabolism* / Q000493:pharmacokinetics; D015687:Cell Hypoxia; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D014217:Troleandomycin / Q000494:pharmacology
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D005296:Ferrous Compounds; D001971:Bromocriptine; D003577:Cytochrome P-450 Enzyme System; D014217:Troleandomycin; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D010100:Oxygen; D000640:Amitrole