Pharmacokinetics of a triphasic oral contraceptive containing desogestrel and ethinyl estradiol.

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.