THE EFFECT OF SPIRONOLACTONE ON DRUG METABOLISM BY HEPATIC MICROSOMES

Abstract

Spironolactone pretreatment of rats (100 mg/kg twice a day for four days) resulted in an induction of hepatic microsomal enzyme activity. The induction differed from the phenobarbital or methylcholanthrene induction in that it did not increase cytochrome P-450 content or microsomal protein. Furthermore the induction seemed to be sex dependent. Thus, ethylmorphine N-demethylation, hexobarbital oxidation and 3,4-benzpyrene hydroxylation were increased 2- to 4-fold in female rats, but of these activities only ethylmorphine N-demethylase was increased in male rats. Cytochrome c reductase activity increased in both sexes. Experiments with methyltestosterone-treated female rats and castrated males indicated that spironolactone might inhibit the effect of endogenous androgenic steroids on liver microsomal enzymes and at the same time exert its own inducing effects.