Pharmacokinetic comparison of two triphasic oral contraceptive formulations containing levonorgestrel and ethinylestradiol

The pharmacokinetics of levonorgestrel (LNG) and ethinylestradiol (EE 2) were determined in 24 women (aged 21 to 35 years), following the administration of a single tablet from the second phase of two different triphasic preparations (Triphasil (R) and Trinordiol (R). Each tablet contained 0.075 mg of LNG and 0.040 mg of EE 2. The data were compared to the pharmacokinetics of LNG and EE 2 obtained following the oral administration of a hydroalcoholic solution (standard) containing the same steroids and dose. The study consisted of a randomized design in which the three formulations were administered to each of the 24 subjects in a three-period crossover pattern. Blood samples were taken at frequent intervals after dosing. Serum levels of LNG and EE 2 were measured by specific radioimmunoassays. The results show that both LNG and EE 2 in the Triphasil and Trinordiol tablets are bioeguivalent with respect to rate and extent of absorption. Furthermore, LNG, but not EE 2, in both tablet formulations was bioequivalent to the solution dose. The serum concentration-time profiles for the three formulations showed that the range of mean peak levels was 2.3–2.8 ng/ml for LNG and 116–159 pg/ml for EE 2. These levels were achieved within 2 hours in the majority of subjects. The ranges of mean values calculated for the areas under the curves were 15–16 ng.hr/ml for LNG and 1053–1390 pg.hr/ml for EE 2. The ranges of mean values calculated for other pharmacokinetic parameters were: volume of distribution: LNG — 1.6–1.8 L/kg, EE 2 — 7.7–9.1 L/kg; clearance: LNG — 84–88 ml/hr/kg, EE 2 — 0.67–0.99 ml/hr/kg; half-life: LNG — 13–15 hr, EE 2 — 7–12 hrs.