Pharmacokinetics of ethinyloestradiol in 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 EE2 in plasma samples in order to avoid the interferences of natural oestrogens. After compartmental analysis, the disposition of EE2 was well described by a two-cpmpartmental open model with mean values of: α = 0.3448 ± 0.2922, 0.1965 ± 0.1755, 0.3058 ± 0.1225 m-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 Vss 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 Vss as a function of dose, but these differences were significant differences in AUC or CI values obtained by compartmental and non-compartmental analysis.