Pharmacokinetics of ethinylestradiol and levonorgestrel after administration of two oral contraceptive preparations.

Serum concentration profiles and pharmacokinetic parameters of ethinyl estradiol (EE2) and levonorgestrel (LNG) were obtained after administration of 2 combined oral contraceptives (OCs). The constituents of the preparations were as follows: Gravistat (0.05 mg EE2 0.125 mg LNG); Minisiston (0.03 mg EE2 0.125 mg LNG). Blood samples were taken before and up to 36 hours after intake of a single tablet by 20 volunteers. In 11 women the investigation was conducted on day 21 of a treatment cycle (steady-state condition). In spite of pronounced interindividual variations of the pharmacokinetic data a clear dependency of EE2 concentration curves on estrogen dose of the respective preparation could be demonstrated. With the condition of steady-state (21st day of administration) there was a slight but significant rise of EE2 peak serum concentrations and a pronounced increase in LNG levels closely reflected by the elevation of the area under curve values. Sex hormone binding globulin (SHBG) serum concentration was significantly increased by day 10 of treatment in all those receiving Gravistat whereas the mean value in the Minisiston group did not change remarkably. Although LNG is known to be bound to SHBG with high affinity the missing parallelism between LNG and SHBG concentrations suggests other possibly additional mechanisms for the elevated LNG-binding capacity in those women taking combined EE2-LNG preparations. (authors modified)