| 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. | |
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MedLine Citation:
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PMID: 9178193 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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K Matsubayashi; H Matsumoto; Y Fukui |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 49 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 1997 May |
Date Detail:
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Created Date: 1997-09-02 Completed Date: 1997-09-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0376363 Medline TA: J Pharm Pharmacol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 551-7 Citation Subset: IM |
Affiliation:
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Department of Legal Medicine, Kyoto University Faculty of Medicine, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amitrole
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pharmacology Animals Aryl Hydrocarbon Hydroxylases* Body Fluid Compartments Bromocriptine / metabolism*, pharmacokinetics Cell Hypoxia Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme System / antagonists & inhibitors, metabolism* Enzyme Inhibitors / pharmacology Ferrous Compounds / pharmacology* Liver / enzymology, metabolism* Male Oxidation-Reduction Oxidoreductases, N-Demethylating / antagonists & inhibitors, metabolism* Oxygen / metabolism, pharmacology* Perfusion Rats Rats, Wistar Troleandomycin / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Ferrous Compounds; 25614-03-3/Bromocriptine; 2751-09-9/Troleandomycin; 61-82-5/Amitrole; 7782-44-7/Oxygen; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/Cytochrome P-450 CYP3A; EC 1.5.-/Oxidoreductases, N-Demethylating |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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