PHARMACOKINETICS OF ESTRADIOL, FREE AND TOTAL ESTRONE, IN YOUNG-WOMENFOLLOWING SINGLE INTRAVENOUS AND ORAL-ADMINISTRATION OF 17-BETA-ESTRADIOL

The pharmacokinetic parameters of estradiol (E2, CAS 50-28-2), free an d total estrone (E1, CAS 53-16-7) were determined in 14 young women fo llowing 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 co mparison with 4 treatments. The purpose of the study was to determine the absolute bioavailability of orally administered E2 in a larger gro up of women and to assess the inter- and intraindividual variability o f basic pharmacokinetic parameters of E2 and metabolically derived E1. In additon, the outcome of this study should provide a basis for the decision whether E2 could potentially be used in a combination oral co ntraceptive There was a dose proportional increase in the AUC-values f ollowing 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 expec ted values were found for E2, free and total E1, respectively. Especia lly the reduction in total E1 concentrations points to an incomplete a bsorption of E2 at the high dose level. The absolute bioavailability o f 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 concentra tions 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. P harmacokinetic parameters, like AUC derived from serum level-time curv es of E2, free and total E1 showed a high intra- and interindividual v ariability. The AUC values calculated for total E1 were less variable than those calculated for E2 and free E1. Because of the very low bioa vailability of oral E2 on the one hand and the high inter- and intrain dividual variability of estrogen levels in the serum on the other hand , E2 seems not to be a likely alternative to ethinylestradiol as the e strogenic component in a combination oral contraceptive.