Sex differences in the effects of microsomal enzyme inducers on hepatic phase I drug metabolism in the rat.

This study investigates the sex-dependence of the effects of microsomal enzyme inducers (phenobarbitone, isosafrole and ethanol) on the hepatic phase I metabolism of lignocaine and imipramine. It is shown that all of the inducers exert sex-dependent effects on the enzymes activities known to be sex related in the rat, e.g. lignocaine N-deethylase activity is decreased by phenobarbitone pretreatment in the male but increased by the same treatment in the female. The inducers tend to decrease the sex differences seen in untreated animals. Ethanol may give this effect by its action of decreasing serum testosterone levels but the mechanism of action of the other compounds is uncertain. It is possible that the sex-dependent cytochrome P-450 species are selectively sensitive to the action of the compounds in terms of induction, repression or inhibition. It is clear, however, that the effects of the pretreatments are related to the sex differences in phase I metabolism in the rat.