Objective: To demonstrate that pharmacokinetic measurements were made at steady state. Subsequently, dose proportionality for desogestrel and ethinyl E2 kinetics were demonstrated.
Design: Open-label, noncomparative study.
Setting: Healthy volunteers in an academic research environment.
Participants: Twenty white women who were 19 to 32 years old were solicited via an advertisement. Nineteen of the 20 women completed the study.
Interventions: Study medication consisted of three cycles of a triphasic oral contraceptive containing desogestrel and ethinyl E2. Blood samples were taken at baseline and during cycle 3 between -48 and 24 hours on days 1, 7, 14, and 21, with additional sampling times on day 21 at 48, 60, and 72 hours.
Main outcome measures: Serum concentrations of 3-keto-desogestrel and ethinyl E2.
Results: Evaluation of the trough serum levels indicated that a steady state of 3-keto-desogestrel had been reached. Statistical analysis on the Cmax, area under the curve (AUC), and Css,min indicated dose proportionality for the administered desogestrel. Ethinyl E2 serum levels obtained at the same time points also reflected steady state levels and showed minimal variability. The statistical analysis on Cmax, AUC, Css,min, and Tmax indicated that the pharmacokinetics of ethinyl E2 on days 7, 14, and 21 were not statistically significantly different, indicating dose equivalency.
Conclusions: Steady state of 3-keto-desogestrel is reached after each of the three phases and the pharmacokinetics are dose proportional. After reaching steady state, the pharmacokinetics of ethinyl E2 remain constant over time.
PIP: This article presents the results of an open-label, noncomparative study analyzing the effects of three different combinations of a triphasic oral contraceptive (OC) containing desogestrel and ethinyl estradiol (ethinyl E2) in 20 healthy White female volunteers. Each study subject was required to pass a physical examination, which included Papanicolaou smear, serological analysis, and urinalysis. The mean age of the study group was 25.1 years. The mean body weight was 143.0 pounds (64.9 kg). The study administration series consisted of tablets containing three combinations of desogestrel and ethinyl E2 (desogestrel/ethinyl E2: 50/35 mcg, 100/30 mcg, and 150/30 mcg). The dosage schedule was 7/7/7, that is, a different dose for each 7-day period. This was followed by a 7-day medication-free period to reflect a 28-day cycle. Venous blood was taken and analyzed for 3-keto-desogestrel, ethinyl E2, and sex hormone-binding globulin (SHBG). This was performed for 3 menstrual-equivalent cycles. Evaluation of the serum levels for 3-keto-desogestrel was proportional to each combined OC dosage. This was also true for ethinyl E2. Dose equivalency was indicated for ethinyl E2, as the three dosage regimens were not different or statistically significant. In this study, use of a triphasic oral contraceptive containing desogestrel and ethinyl E2 resulted in a statistically significant increase in SHBG serum levels between cycle day 7 and 21 (185.5 +or- 32.1 vs. 205.6 +or- 21.9 mmol/L).