PHARMACOKINETICS OF ETHINYLESTRADIOL IN RABBITS AFTER INTRAVENOUS ADMINISTRATION

The pharmacokinetics of ethinyloestradiol (EE(2)) after intravenous ad ministration of 30, 50 and 100 mu g.kg(-1) was investigated in rabbits . A high-performance liquid chromatographic (HPLC) method with electro chemical (EC) detection was used to measure EE(2) in plasma samples in order to avoid the interferences of natural oestrogens. After compart mental analysis, the disposition of EE(2) was well described by a two- compartmental open model with mean values of: alpha = 0.3448 +/- 0.292 2, 0.1965 +/- 0.1755, 0.3058 +/- 0.1225 min(-1), and beta = 0.0137 +/- 0.0018, 0.0140 +/- 0.0065, 0.0198 +/- 0.0066 min(-1), for the three d oses studied, respectively. There were no dose-related differences (AN OVA, P < 0.05) in a, b or V-ss, but significant differences were detec ted in clearance (90.9 +/- 18.7; 80.6 +/- 17.6; 116.3 +/- 22.5 ml.min( -1).kg(-1)) between the 100 mu g.kg(-1) group and lower dose groups. T he 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 anal ysis there were no significant differences in lambda, MRT or V-ss as a function of dose, but these differences were significant when Cl or A UC were compared. There were no significant differences in AUC or Cl v alues obtained by compartmental and non-compartmental analysis.