Pharmacokinetic Interpretation of Plasma Cortisol and Cortisone Concentrations Following a Single Oral Administration of Cortisone Acetate to Human Subjects

Abstract

The pharmacokinetic and biopharmaceutic profiles of a single dose of oral cortisone acetate were developed for 23 healthy normal adult volunteers using cortisone and cortisol plasma concentration data. Cortisone acetate was rapidly absorbed and converted to the therapeutic moiety cortisol. There was a linear increase in plasma concentrations and, therefore, areas under the plasma concentration-time curves with increasing doses of 5, 10 and 25 mg. Doses (25 mg) given as 1 .times. 25 mg or 5 .times. 5 mg were bioequivalent. The increased efficacy of oral over i.m. cortisone acetate can be attributed to the increased conversion to cortisol as a result of 1st-pass metabolism following oral dosing.