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 estradiol (E2) 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 E2 and estrone (E1) serum concentrations were determined using commercially available immunoassay kits. Bioequivalence testing was performed between the following oral formulations: (a) 1.5 mg E2 tablets versus 2 mg E2V tablets; and (b) 1.5 mg E2 plus 0.15 mg DSG tablets versus 1.5 mg E2 tablets.


RESULTS
For both E2 and E1 the E2 tablet was bioequivalent with both the E2V and the E2/DSG tablet with respect to the rate and extent of absorption (bioavailability). Although the mean tmax values of the three tablet formulations were similar, the variability was too large to prove formal bioequivalence.


CONCLUSIONS
E2 tablets and E2/DSG tablets were bioequivalent and also bioequivalence of E2 tablets with commercially available E2V was found, which ensures a sequential HRT preparation without large variations in estrogen serum concentrations.
Department of Drug Metabolism and Kinetics, NV Organon, Oss, The Netherlands.
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CJ
Timmer
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Geurts
D000368:Aged; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D004958:Estradiol / Q000097:blood*; D004970:Estrone / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D013607:Tablets / Q000493:pharmacokinetics
D013607:Tablets; D004970:Estrone; D004958:Estradiol