Disposition of maternally-administered methadone and its effects on hepatic drugmetabolizing functions in perinatal guinea pigs

Abstract

Racemic methadone HC1 (25 mg/kg given every 12 hr for 2 consecutive days) was administered orally to pregnant (60–65 days of gestation) or nursing (0–8 days post-partum) albino guinea pigs. The dams, fetuses and pups were killed 12 hr after the last dose for the anaysis of maternal and perinatal plasma, brain, hepatic and renal methadone residues by GLC and the in vitro measurement of maternal and perinatal microsomal mono-oxygenase [ p-nitroanisole O-demethylase (OD) and aniline hydroxylase (AH)] and glucuronosyltransferase (GT) activities. Methadone was acquired by the perinatal guinea pig both transplacentally and via the milk, more agent being obtained by the former route. Fetal plasma levels of methadone were consistently lower than those detected in the mother due, largely, to differential plasma protein binding. The perinatal pattern of tissue distribution of methadone was markedly different from that observed in the dam, exceedingly high levels being found in fetal brain and kidney. Maternally-administered methadone did not affect the ontogenesis of perinatal OD, AH and GT but it did reduce significantly the levels of hepatic GT activity in the pups and in the dams.