Age-related changes in metabolism of diethofencarb: Relationship between metabolism in rat and hepatic drug-metabolizing enzyme activities

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Abstract
1. Age-related changes in metabolism of diethofencarb (DFC) (isopropyl-1,4-diethoxycarbanilate) and hepatic drug-metabolizing enzyme activities were studied in male Sprague-Dawley rats aged 2, 8, 16 and 21 months. 2. Following a single oral dose of 14C-DFC (500 mg/kg), the major route of elimination of the 14C for 7 days was urine (85.6-97.8%) at all ages. 3. Analysis of urinary metabolites showed that deethylation of 14C-DFC was constant for all age groups; however, sulphation and acetylation significantly decreased, and glucuronidation increased, with age. 4. Hepatic PAPS-sulphotransferase and acetyl-CoA: N-acetyltransferase in DFC metabolism significantly decreased with age, whereas no significant effects of ageing on O-deethylase and UDP-glucuronyltransferase were observed. 5. Results show that age-related differences in the ratios of urinary metabolites of DFC resulted to some extent from changes in the hepatic drug-metabolizing enzyme activities.