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.
Kuhnz
W
W
Research Laboratories, Berlin, Germany.
Hümpel
M
M
Biere
H
H
Gross
D
D
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002247:Carbon Isotopes; D045166:Estradiol Congeners / Q000493:pharmacokinetics*; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous
D002247:Carbon Isotopes; D045166:Estradiol Congeners; D004997:Ethinyl Estradiol