THE EFFECT OF CYPROTERONE ACETATE PRETREATMENT ON THE IN VITRO METABOLISM OF ANILINE, HEXOBARBITAL AND ³H-DIGITOXIGENIN

¹ Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Nebraska-Lincoln, Lincoln, Nebraska

Cyproterone acetate (50 mg/kg) spironolactone (100 mg/kg) and isotonic saline were administered to separate groups of male and female rats daily for four days. Microsomes then obtained from the cyproterone acetate- and spironolactone-pretreated males and females showed enhanced aniline metabolism compared to corresponding control groups. Both Drugs enhanced the metabolism of hexobarbital by female rat liver microsomes and decreased it in the male. Neither drug seemed to exert these effects through enhanced synthesis on decreased breakdown of cytochrome P-450. A possible relationship between antiandrogenicity and drug metabolism is discussed based on the results of this inivestigation and previous studies on the intracellular mechanism of cyproterone acetate. Both cyproterone acetate and spironolactone increased the total production of polarmetabolites of ³H-digitoxigenin in liver homogenates obtained from rats of either sex. This finding may be germane to investigations concerning the mechanism by which spironolactone protects the rat against chronic digitoxin toxicity.