Bioavailability and pharmacokinetics of cyproterone acetate after oral administration of 2.0 mg cyproterone acetate in combination with 50 μg ethinyloestradiol to 6 young women

Abstract

Six female volunteers were given single oral doses of 2.0 mg 14C-labelled cyproterone acetate and 50 μg−3H-labelled ethinyloestradiol as lactose micronisate in gelatine capsules. Elimination of 14C-labelled material with urine and faeces was measured for 10 days post-administration, the concentration of 14C-labelled substance(s) and of cyproterone acetate in plasma (RIA) until 5 days post-administration. 1.1. Cyproterone acetate reached a maximum plasma level of 7.2 ± 1.4 ng/ ml after about 4 hours. Postmaximum disposition took place in two phases with half-lives of 3.0 ± 1.3 hours and 2.0 ± 0.4 days, respectively. An apparent volume of distribution (Vf) of 1300 ± 580 litres was calculated for cyproterone acetate.2.2. Despite higher absolute values (maximum value after 3 12hours: 18.6 ± 3.8 ng/ml), plasma cyproterone acetate-14C equivalents showed a similar course of concentration to the unchanged drug with half-lives of 3.0 ± 1.6 hours and 1.7 ± 0.5 days, respectively. Recovery was 88 ± 11 % of the dose and 30.4 ± 7.3 % of the dose was eliminated with urine. The elimination half-life was 1.8 ± 0.1 days.3.3. Concentration of the main metabolite of cyproterone acetate in plasma (difference between ng 14C equivalents/ml and ng cyproterone acetate/ml) declined in accordance with the terminal disposition phase of cyproterone acetate with a half-life of 1.9 ± 0.7 days. An apparent volume of distribution (Vf) of 95 ± 25 litres was estimated for the main metabolite.As compared with its main metabolite, cyproterone acetate has 10 times the apparent volume of distribution and about 90 % is present as unchanged drug at all times after administration. After the end of distribution (0.5 days post-administration), the proportion of the drug in terms of total activity in plasma remains constant. Presumably retransfer of the drug from tissues is the rate-determining step in the metabolization of cyproterone acetate and the elimination of metabolites.