Pharmacokinetics of estradiol, free and total estrone, in young women following single intravenous and oral administration of 17 beta-estradiol.

The pharmacokinetic parameters of estradiol (E2, CAS 50-28-2), free and total estrone (E1, CAS 53-16-7) were determined in 14 young women following a single oral administration of 2, 4 and 8 mg E2 and a single intravenous administration of 0.3 mg E2 in an open, intraindividual comparison with 4 treatments. The purpose of the study was to determine the absolute bioavailability of orally administered E2 in a larger group of women and to assess the inter- and intraindividual variability of basic pharmacokinetic parameters of E2 and metabolically derived E1. In addition, the outcome of this study should provide a basis for the decision whether E2 could potentially be used in a combination oral contraceptive. There was a dose proportional increase in the AUC-values following the oral administration of 2 mg and 4 mg doses of E2. At the high dose of 8 mg, however, only about 76%, 78% and 70% of the expected values were found for E2, free and total E1, respectively. Especially the reduction in total E1 concentrations points to an incomplete absorption of E2 at the high dose level. The absolute bioavailability of orally administered E2 was calculated based on the 4 mg dose and was found to be 4.9 +/- 5.0%. The mean ratio of free E1 and E2 concentrations in the serum, following parenteral and oral administration of E2 was about 1.0 (i.v.) and between 8.8 to 19.8 (p.o.), respectively. Pharmacokinetic parameters, like AUC, derived from serum level-time curves of E2, free and total E1 showed a high intra- and interindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)