Dose-Related and Other Effects of Maternal Cimetidine Pretreatment during Lactation on Drug Metabolism in Mouse Dams and Pups

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Abstract
The effects of maternal cimetidine pretreatment at different dose levels during lactation, on drug metabolism, were investigated in mouse dams and recently weaned pups. Aminopyrine N-demethylase, aniline hydroxylase and pentobarbitone metabolism were inhibited in both dams and pups in a dose-dependent manner (15, 25 and 50 mg/kg/day, i.p.). Pretreatment at a dose level of 50 mg/kg/day resulted in comparable levels of inhibition of drug metabolism in dams and female pups while male pups were less affected. Of the three indices studied, aniline hydroxylase was the least influenced by cimetidine pretreatment. Thus, the effects of maternal cimetidine pretreatment on drug metabolism in the nursing pair varied with the dose, sex and substrate. The possible implications of these results for man are discussed.