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In 8 female sports students (runners) aged 20 and 21 years and 10 women between 20 and 40 years of age, who regularly underwent body building training, serum levels of ethinylestradiol (EE2) and levonorgestrel (LNG) have been determined under conditions of exercise as well as in rest, prior to and following the intake of 1 tablet of Gravistat (0.05 mg EE2, 0.125 mg LNG). Blood samples were obtained at points 0, 2, 6 and 24 hours. Exercise (5000 meter running and intensive body building training of one hour duration, respectively) was started immediately after intake of the steroid combination. There were no significant differences in the serum concentration levels obtained during exercise and rest. But exercise consistently resulted in a slight decrease of EE2 and LNG serum concentrations and the area under curve values.

Pharmacokinetic investigations (c0h, c2h, c6h, c24h, AUC24) were carried out both in the first and last four days of a treatment cycle in patients of different ages, who used oral contraceptives at least for 12 months. 57 women took the preparation Trisiston (three-step-formulation with the components 0.03 mg ethinylestradiol (EE2) + 0.05 mg levonorgestrel (LNG), 0.04 mg EE2 + 0.075 mg LNG, 0.03 mg EE2 + 0.125 mg LNG), 23 subjects used Gravistat (0.05 mg EE2 + 0.125 mg LNG) and 17 patients were under Certostat, a preparation still in clinical evaluation (0.05 mg EE2 + 2.0 mg Dienogest (DNG)). The levels of EE2, LNG and DNG were measured by means of radioimmunoassays. Between the concentrations obtained after administration of a first and single tablet (earlier investigations) and those determined in long-time users during the first 4 days following the tablet-free interval no qualitative and quantitative differences were observed. Between the levels of EE2 and LNG determined in the first and last days of the treatment cycle, marked differences were found in patients under the formulations Trisiston and Gravistat, but not in those taking Certostat. It is concluded that a cyclic and reversible cumulating effect emerges under the influence of LNG-containing contraceptives, the mechanism of which cannot be explained solely by the increase of carrier protein capacity. It seems possibly due to an alteration of steroid metabolism resulting from the interaction between both components.

Serum levels of ethinylestradiol (E2) and levonorgestrel (LNG) have been determined in 10 volunteers of similar age after administration of 1 tablet of the oral contraceptives Gravistat and Ediwal, respectively, each containing 0.05 mg E2 and 0.125 mg LNG, using a cross over design. The studies were carried out at intervals of 4 weeks, within the follicular phase of the menstrual cycle and under standardized conditions. Wide variations were observed between the women in the calculated pharmacokinetic parameters, while there was a relatively close correspondence between the intra-individually obtained values, except for one case.

A radioimmunoassay for ethinylestradiol (EE2) which was developed in the pharmacological department of VEB Jenapharm has been modified and fully validated. It was the purpose of the present study to extend the still limited data concerning EE2-serum levels after a single and repeated ingestion of combination pills with different doses of EE2. 10 volunteers aged 17-25 years with normal body weight and length received a single tablet of either Gravistat (0.05 mg ethinylestradiol + 0.125 mg levonorgestrel) or Minisiston (0.03 mg ethinylestradiol + 0.125 mg levonorgestrel). 11 other women were involved into the study after ingestion of the 21st tablet of a contraceptive cycle. Peak serum levels which were significantly higher in the Gravistat- than in the Minisiston-group were observed 90 to 120 minutes after the oral administration. Detectable EE2 levels were determined in all volunteers after 24 hours. Pharmacokinetic data showed pronounced interindividual variations. Whereas the mean 24 hours levels of EE2 increased progressively during the treatment cycles, kinetic values obtained at the end of the cycle exhibited a significantly higher level than those after ingestion of a single dose. Area under curve (AUC) was calculated by the trapezoidal rule with the aid of a compartment free model.