Effect of N-Phenylbarbital (Phetharbital) on the Metabolism of Testosterone and Cortisol in Man

ABSTRACT The effect of phetharbital on testosterone and cortisol metabolism was studied in a normal man and woman and in a woman with Cushing's syndrome due to nontumorous adrenocortical hyperfunction. Administration of the drug resulted in a moderate decrease in the metabolic clearance and plasma production rates of testosterone. In addition, there occurred an appreciable decrease in the urinary excretions of androsterone, etiocholanolone and the 11-oxyketosteroids, associated with an increased excretion of polar metabolites of testosterone. The latter metabolites have not been identified. However, chromatographic studies have excluded the following steroids from contributing to the polar fraction: testosterone, 6β-hydroxytestosterone, 7α-hydroxytestosterone, 16α-hydroxytestosterone, androstenediol and 5α-and 5β-androstanediol. The administration of phetharbital also resulted in a sharp increase in the urinary excretion of the polar cortisol metabolite, 6β-hydroxycortisol.