INVESTIGATION INTO THE AGE-DEPENDENCE OF THE PHARMACOKINETICS OF CYPROTERONE-ACETATE IN HEALTHY MALE-VOLUNTEERS

Objective: To investigate a possible age-dependence of the pharmacokin etics of cyproterone acetate following single oral administration. Met hods: Twenty eight healthy men between 22 and 74 years of age received a single oral dose of 100 mg cyproterone acetate. The pharmacokinetic parameters, area under the serum concentration-time curve, apparent v olume of distribution, apparent clearance, terminal half-life and the concentration ratio of 15 beta-hydroxy-cyproterone acetate/cyproterone acetate were examined for possible age-dependence using regression an alysis. Results: The values of area under the serum level-time curve s howed high interindividual variability and were not related to age. Wi th regard to apparent clearance and volume of distribution, decreasing and increasing values, respectively, were observed with increasing ag e. There was also a clear dependence of the terminal half-life on age. Elderly men had values about two times higher (95 h) than men belongi ng to the younger age groups (45 h). The mean concentration ratio of 1 5 beta-hydroxy-cyproterone acetate/cyproterone acetate was 0.8 (0.3) a nd showed no age-dependent change. Conclusions: Apparent clearance and apparent volume of distribution of cyproterone acetate showed age-dep endent changes. Combined, the two effects cause a clear age-dependence of the terminal half-life of cyproterone acetate. An age-related redu ction in liver volume is thought to be mainly responsible for the decr ease in hepatic clearance with age. Chronic daily administration of th e drug to elderly men may therefore lead to somewhat higher steady-sta te concentrations in the serum than in young men receiving the same do se.