Journal article
Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats
Journal of pharmacy and pharmacology, Vol.56(6), pp.819-825
06/2004
Handle:
https://hdl.handle.net/2376/115523
PMID: 15231049
Abstract
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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Details
- Title
- Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats
- Creators
- Jill S Warrington - Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, MA 02111, USAMichael H CourtDavid J GreenblattLisa L von Moltke
- Publication Details
- Journal of pharmacy and pharmacology, Vol.56(6), pp.819-825
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- England
- Grant note
- DA-13834 / NIDA NIH HHS GM-61834 / NIGMS NIH HHS DA-05258 / NIDA NIH HHS AG-17880 / NIA NIH HHS DK/AI-58496 / NIDDK NIH HHS RR-00054 / NCRR NIH HHS AT-01381 / NCCIH NIH HHS DA-13209 / NIDA NIH HHS MH-58435 / NIMH NIH HHS
- Identifiers
- 99900547440801842
- Language
- English
- Resource Type
- Journal article