Pharmacokinetics of ethinyloestradiolin rabbits after intravenous administration

Abstract

The pharmacokinetics of ethinyloestradiol (EE 2) after intravenous administration of 30, 50 and 100 μg.kg −1 was investigated in rabbits. A high-performance liquid chromatographic (HPLC) method with electrochemical (EC) detection was used to measure EE 2 in plasma samples in order to avoid the interferences of natural oestrogens. After compartmental analysis, the disposition of EE 2 was well described by a two-compartmental open model with mean values of: α = 0.3448 ± 0.2922, 0.1965 ± 0.1755, 0.3058 ± 0.1225 min −1, and β = 0.0137 ± 0.0018, 0.0140 ± 0.0065, 0.0198 ± 0.0066 min −1, for the three doses studied, respectively. There were no dose-related differences (ANOVA, P < 0.05) in a, b or V ss, but significant differences were detected in clearance (90.9 ± 18.7; 80.6 ± 17.6; 116.3 ± 21.5 ml.min −1.kg −1) between the 100 μg.kg −1 group and lower dose groups. The AUC increased significantly with the doses (341.7 ± 67.1; 645.8 ± 143.9; 892.2 ± 211.9 ng.min.ml −1). After non-compartmental analysis there were no significant differences in λ, MRT or V ss as a function of dose, but these differences were significant when Cl or AUC were compared. There were no significant differences in AUC or Cl values obtained by compartmental and non -compartmental analysis.