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 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.
Saito
K
K
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., Osaka, Japan.
Kaneko
H
H
Sato
K
K
Yoshitake
A
A
Yamada
H
H
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002219:Carbamates / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes; D008099:Liver / Q000201:enzymology*; D008297:Male; D048448:Phenylcarbamates; D051381:Rats; D011919:Rats, Inbred Strains
D002219:Carbamates; D002250:Carbon Radioisotopes; D048448:Phenylcarbamates; C070961:diethofencarb