Potentiation of Cortisol Induction of Hepatic Tyrosine Transaminase by β-Diethylaminoethyl Diphenylpropylacetate

Abstract

β-DIETHYLAMINOETHYL diphenylpropylacetate (SKF 525A) has been demonstrated in the rat to inhibit the metabolism of drugs both in vitro and in vivo^1,2. We have demonstrated that the conversion of cortisol to a polar metabolite or metabolites by the 9,000g supernatant of the male rat liver is inhibited by the addition of SKF 525A to the incubation mixture³. The similarity between liver enzymes which metabolize drugs and those which hydroxylate steroids⁴ suggested the possibility that SKF 525A would inhibit the hydroxylation of cortisol in vivo. In turn, it was thought that this inhibition could manifest itself in an increase in the biological activity of administered cortisol. The administration of cortisol is known to increase the activity of rat liver tyrosine transaminase^5,6. The present investigation demonstrates in the male rat a further increase in cortisol induction of tyrosine transaminase by SKF 525A.