Methadone hydrochloride: acute administration, disposition and effects on hepatic function in guinea pigs.
d,1-Methadone hydrochloride was administered orally to adult female albino guinea pigs at a dose of 25 mg/kg body weight every 12 h for 10 consecutive days. Twelve hours after a dose, subgroups of animals were sacrificed at 2, 5 and 10 days for tissue (blood plasma, brain, liver and kidney) methadone residue analysis and the in vitro measurement of hepatic microsomal p-nitroanisole O-demethylase (OD), aniline hydroxylase (AH) and glucuronosyltransferase (GT) activities. No overt toxicity was observed during treatment other than a decrease in body weight. Withdrawal signs were absent during the 14-day post-treatment regression period. Tissue methadone levels were constant except for a decreased concentration in the liver at 5 and 10 days. No effect on hepatic OD and AH was observed during treatment but a significant decrease in GT activity was measured which returned to normal values 14 days after terminating treatment.
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008691:Methadone / Q000378:metabolism / Q000633:toxicity*
D008691:Methadone