Pharmacokinetics of Ethinylestradiol and Levonorgestrel after Administration of Two Oral Contraceptive Preparations

Abstract

Serum concentration profiles and pharmacokinetic parameters (cmax, tmax, AUC24, AUC0-00, MRT) of ethinylestradiol (EE2) and levonorgestrel (LNG) were obtained following administration of two combined oral contraceptives. 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). In 20 of the volunteers blood samples were taken before and up to 36 hours following the intake of a single table. In 11 women the investigation was carried out at 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 the estrogen dose of the respective preparation could be demonstrated. Under the condition of steady-state (21st day of administration) there was a slight but significant rise of the EE2 peak serum concentrations and a pronounced increase of the LNG levels, closely reflected by elevation of the AUC values. SHBG serum concentration was significantly increased by the 10th day of treatment in all subjects receiving Gravistat, whereas the mean value in the Minisiston-group did not remarkably change. Although LNG is known to be bound to SHBG with high affinity, the missing parallelism between LNG- and SHBG-concentrations suggests other (additional?) mechanisms for the elevated LNG-binding capacity in women taking combined EE2-LNG preparations.