Bioequivalence assessment of three different estradiol formulations in postmenopausal women in an open, randomized, single-dose, 3-way cross-over study

Objective: the aim of the study was to assess the bioavailability of estrad iol (E-2) following oral, single-dose administration of equimolar doses of three HRT preparations in a 3-way cross-over study in postmenopausal women. Methods: 18 healthy subjects were enrolled. Free E-2 and estrone (E-1) seru m concentrations were determined using commercially available immunoassay k its. Bioequivalence testing was performed between the following oral formul ations: (a) 1.5 mg E-2 tablets versus 2 mg E2V tablets; and (b) 1.5 mg E-2 plus 0.15 mg DSG tablets versus 1.5 mg E-2 tablets. Results: for both E-2 and E-1, the E-2 tablet was bioequivalent with both t he E2V and the E-2/DSG tablet with respect to the rate and extent of absorp tion (bioavailability). Although the mean t(max) values of the three tablet formulations were similar, the variability was too large to prove formal b ioequivalence. Conclusion: E-1 tablets and E-2/DSG tablets were bioequivalent and also bio equivalence of E-2 tablets with commercially available E2V was found, which ensures a sequential HRT preparation without large variations in estrogen serum concentrations.