Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats.

Article Details

Citation

Warrington JS, Court MH, Greenblatt DJ, von Moltke LL

Phenacetin and chlorzoxazone biotransformation in aging male Fischer 344 rats.

J Pharm Pharmacol. 2004 Jun;56(6):819-25.

PubMed ID
15231049 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
ChlorzoxazoneCytochrome P450 1A1ProteinHumans
Unknown
Substrate
Details