| Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats. | |
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MedLine Citation:
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PMID: 15231049 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We evaluated the role of specific isoforms in the biotransformation of phenacetin and chlorzoxazone and examined the effect of age on these reactions using liver microsomes from Fischer 344 rats between 3 and 26 months of age. Using rat cDNA-expressed cytochrome P450 (CYP) enzymes, we found that phenacetin biotransformation was primarily mediated by CYP2C6 and CYP1A isoforms, while chlorzoxazone biotransformation was largely mediated by CYP2E1 and CYP1A1. Incubations with liver microsomes prepared from rats of varying ages demonstrated that both phenacetin and chlorzoxazone biotransformation declined with age. Metabolite formation rates in the old rats (25-26 months) were reduced by approximately 60-70% for these reactions. This study suggests that the activity of CYP2E and CYP1A enzymes decline with age in the rat liver. Also, the relative specificity of the index substrates phenacetin (for CYP1A2) and chlorzoxazone (for CYP2E1) in man appears not to be applicable in rats. |
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Authors:
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Jill S Warrington; Michael H Court; David J Greenblatt; Lisa L von Moltke |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of pharmacy and pharmacology Volume: 56 ISSN: 0022-3573 ISO Abbreviation: J. Pharm. Pharmacol. Publication Date: 2004 Jun |
Date Detail:
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Created Date: 2004-07-02 Completed Date: 2004-11-10 Revised Date: 2007-11-14 |
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: 819-25 Citation Subset: IM |
Copyright Information:
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Copyright 2004 The Authors |
Affiliation:
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Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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metabolism* Animals Biotransformation Chlorzoxazone / pharmacokinetics* Chromatography, High Pressure Liquid Cytochrome P-450 Enzyme System / metabolism Isoenzymes / metabolism Male Microsomes, Liver / metabolism Phenacetin / pharmacokinetics* Rats Rats, Inbred F344 |
| Grant Support | |
ID/Acronym/Agency:
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AG-17880/AG/NIA NIH HHS; AT-01381/AT/NCCAM NIH HHS; DA-05258/DA/NIDA NIH HHS; DA-13209/DA/NIDA NIH HHS; DA-13834/DA/NIDA NIH HHS; DK/AI-58496/DK/NIDDK NIH HHS; GM-61834/GM/NIGMS NIH HHS; MH-58435/MH/NIMH NIH HHS; RR-00054/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Isoenzymes; 62-44-2/Phenacetin; 9035-51-2/Cytochrome P-450 Enzyme System; 95-25-0/Chlorzoxazone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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