Disposition of maternally-administered methadone and its effects on hepatic drug-metabolizing functions in perinatal guinea pigs.
Racemic methadone HCl(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 analysis 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.
D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism; D006168:Guinea Pigs; D008099:Liver / Q000201:enzymology*; D008431:Maternal-Fetal Exchange; D008691:Methadone / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding; D014018:Tissue Distribution
D001798:Blood Proteins; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D014453:Glucuronosyltransferase; D008691:Methadone