Plasma levels of active ingredients after single and repeated administration of a new oral contraceptive containing 2 mg of cyproterone acetate and 50 micrograms of ethinyl estradiol (DIANE) to five young women.

Peripheral plasma from five young women was analyzed for cyproterone acetate and ethinyl estradiol during a period of 96 hours duration after single oral intake of a coated tablet of DIANE (2 mg of cyproterone acetate + 50 micrograms of ethinyl estradiol), and during a treatment cycle of 21 days during which the formulation was given daily. Radioimmunoassays were utilized for quantifications. A maximum concentration of 11.0 +/- 3.4 ng of cyproterone acetate/ml plasma was found 1.6 +/- 0.6 hours after a single administration of DIANE. Postmaximal disposition took place in two phases with half-lives of 1.9 +/- 0.6 hours and 2.2 +/- 0.2 days. The maximum level of 0.08 +/- 0.03 ng of ethinyl estradiol/ml plasma was found 1.6 +/- 0.6 hours after such single administration. Following commencement of a daily oral intake of DIANE a steady state was reached by the 5th to 8th days, during which 24 hours after each dose cyproterone acetate concentrations were found to be 2.4 +/- 0.7 times higher than at the corresponding time after a single administration. Accordingly, after the first third of the 21 day treatment cycle an almost constant plasma level was reached indicating an equilibrium of intake and elimination. Except for a change in the mean terminal half life after multiple dosing, there was evidently no change in the kinetics of cyproterone acetate. No pointers to an accumulation of ethinyl estradiol upon daily administration of DIANE could be found.