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 an d ethinyl E(2) kinetics were demonstrated. Design: Open-label, noncomp arative study. Setting: Healthy volunteers in an academic research env ironment. Participants: Twenty white women who were 19 to 32 years old were solicited via an advertisement. Nineteen of the 20 women complet ed the study. Interventions: Study medication consisted of three cycle s of a triphasic oral contraceptive containing desogestrel and ethinyl E(2). 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 t imes on day 21 at 48, 60, and 72 hours. Main Outcome Measures: Serum c oncentrations of 3-keto-desogestrel and ethinyl E(2). Results: Evaluat ion of the trough serum levels indicated that a steady state of 3-keto -desogestrel had been reached. Statistical analysis on the C-max, area under the curve (AUC), and C-ss,C-min indicated dose proportionality for the administered desogestrel. Ethinyl E(2) serum levels obtained a t the same time points also reflected steady state levels and showed m inimal variability. The statistical analysis on C-max, AUC, C-ss,C-min , and T-max indicated that the pharmacokinetics of ethinyl E(2) on day s 7, 14, and 21 were not statistically significantly different, indica ting dose equivalency. Conclusions: Steady state of 3-keto-desogestrel is reached after each of the three phases and the pharmacokinetics ar e dose proportional. After reaching steady state, the pharmacokinetics of ethinyl E(2), remain constant over time.