Effects of cimetidine on drug metabolism in rat pups.

The effects of cimetidine on drug metabolism were studied in male and female rat pups and compared to similar effects in adult rats. As in adult rats, cimetidine 50 mg/kg/day i.p. for 7 days in the 2nd, 3rd, 4th or 5th weeks of life resulted in prolonged pentobarbitone sleeping times (diminished pentobarbitone hydroxylase activities), particularly when administered during the 3rd week. These effects of cimetidine were reversible since they continued only up to 2 weeks in males and 4 weeks in females, but by the 6th week were no longer observed. Pretreatment with cimetidine 15, 25 and 50 mg/kg/day i.p. for 7 days, resulted in a dose-dependent inhibition of aminopyrine N-demethylase and aniline hydroxylase as well as a prolongation of pentobarbitone sleeping time in both pups and adults, aniline hydroxylase being the least affected. In general, female pups were more adversely affected than male pups and adults. The therapeutic and toxicological relevance of these results in man are discussed.