Influence of repeated oral doses of ethinyloestradiol on the metabolic disposition of [C-13(2)]-ethinyloestradiol in young women

Objective: To examine the influence of daily oral administration of ethinyloestradiol on the total clearance of C-13-labeled ethinyloestradiol in women. Methods: 19, healthy young women received a single IV dose of 0.06 mg C-ethinyloestradiol. Subsequently, they were treated with daily oral doses of 0.06 mg ethinyloestradiol for 8 days. On the last day of oral treatment, they received a further IV dose of 0.06 mg C-13-ethinyloestradiol. The pharmacokinetic parameters clearance, area under the serum level-time curve, terminal half-life, steady-state volume of distribution and mean residence time of C-13-ethinyloestradiol in each volunteer were evaluated after both IV doses, and the corresponding pairs of parameters were examined statistically for the significance of intraindividual differences. Results: Following the first (second) intravenous administration, the mean area under the curve was 2.54 (2.67) ng . h . ml(-1). The terminal half-life and mean residence time were 9.7 (9.6)h and 10.5 (10.1) h, respectively. The steady-state volume of distribution was 4.3 (3.9) 1 . kg(-1) and the clearance was 7.0 (6.6) ml . min(-1) . kg(-1). No significant difference was observed in any of these parameters between the first and the second TV doses of C-13-EE(2). Conclusions: Since the clearance in particular remained unchanged after repeated oral administration of ethinyloetradiol, the hypothesis that ethinyloestradiol can inhibit its own metabolism in vivo can be rejected.