RT Journal Article
SR Electronic
T1 l-alpha-Acetylmethadol administration to lactating rat dams. Effect on hepatic aniline hydroxylase and ethylmorphine N-demethylase activities in rat pups.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 9
OP 14
VO 16
IS 1
A1 G A Lesher
A1 W P Beierschmitt
YR 1988
UL http://dmd.aspetjournals.org/content/16/1/9.abstract
AB l-alpha-Acetylmethadol (LAAM) was administered to lactating rat dams, and subsequent effects on hepatic drug-metabolizing enzymes of their offspring were assessed. Dams were given LAAM or a control solution in their drinking water following parturition and throughout lactation. Hepatic ethylmorphine-N-demethylase (EMDM) and aniline hydroxylase (AH) activities, as well as cytochrome P-450 content, were determined in the offspring at 21-23 days of age, or following sexual maturation (61-64 days). LAAM induced AH and EMDM activities, as well as cytochrome P-450 content in both male and female 21-23-day-old pups compared to controls; these differences were not observed at 61-64 days of age. In addition, normal sex-related differences in EMDM activity were apparent at 61-64 days of age. These results demonstrate the LAAM administration to lactating dams causes hepatic metabolic induction in the sexually immature rat, suggesting that LAAM and/or its metabolites passed to the pups via the milk. These changes, induced by LAAM administered via lactation, are reversible and do not interfere with the normal development of sex-dependent differences in hepatic EMDM activity observed in rats following sexual maturation.