AGE-RELATED-CHANGES IN METABOLISM OF DIETHOFENCARB - RELATIONSHIP BETWEEN METABOLISM IN RAT AND HEPATIC DRUG-METABOLIZING ENZYME-ACTIVITIES

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 C-14-DFC (500 mg/kg), the major route of elimination of the C-14 for 7 days was urine (85.6-97.8%) at all ages. 3. Analysis of urinary metabolites showed that deethylation of C-14-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.