Investigation into the age-dependence of the pharmacokinetics of cyproterone acetate in healthy male volunteers

Objective: To investigate a possible age-dependence of the pharmacokinetics of cyproterone acetate following single oral administration. Methods: 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 volume 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 analysis. Results: The values of area under the serum level-time curve showed high interindividual variability and were not related to age. With regard to apparent clearance and volume of distribution, decreasing and increasing values, respectively, were observed with increasing age. 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 belonging to the younger age groups (45 h). The mean concentration ratio of 15 beta-hydroxy-cyproterone acetate/cyproterone acetate was 0.8 (0.3) and showed no age-dependent change. Conclusions: Apparent clearance and apparent volume of distribution of cyproterone acetate showed age-dependent changes. Combined, the two effects cause a clear age-dependence of the terminal half-life of cyproterone acetate. An age-related reduction in liver volume is thought to be mainly responsible for the decrease in hepatic clearance with age. Chronic daily administration of the drug to elderly men may therefore lead to somewhat higher steady-state concentrations in the serum than in young men receiving the same dose.