Influence of repeated oral doses of ethinyloestradiol on the metabolic disposition of [13C2]-ethinyloestradiol in young women.

Objective: To examine the influence of daily oral administration of ethinyloestradiol on the total clearance of 13C-labeled ethinyloestradiol in women.
Methods: 19, healthy, young women received a single IV dose of 0.06 mg 13C-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 13C-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 13C-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 IV doses of 13C-EE2.
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.