BIOEQUIVALENCE OF A 17-BETA-ESTRADIOL HYDROXYPROPYL-BETA-CYCLODEXTRINCOMPLEX IN POSTMENOPAUSAL WOMEN

Five postmenopausal women received single doses of a 0.675 mg estradio l hydroxypropyl-beta-cyclodextrin (estradiol-HPbetaCD) sublingual tabl et by the sublingual and oral route. A single dose of a 1 mg micronize d estradiol tablet was given orally for comparison. Blood samples were obtained over 48 hours for measurement of estradiol, estrone, luteini zing hormone (LH) and follicle-stimulating hormone (FSH) concentration s. Sublingual administration produced faster and significantly higher peak estradiol concentrations than after oral administration of either estradiol-HPbetaCD or micronized estradiol. The concentration-time ar ea under the curve of estradiol after sublingual estradiol-HPbetaCD wa s also significantly larger than after oral administration of either e stradiol-HPbetaCD or micronized estradiol, reflecting a larger estradi ol bioavailability. The estradiol/estrone concentration ratio after su blingual estradiol-HPbetaCD revealed a predominance of estradiol for t he first 2 hours after the dose, followed by an estrone predominance. Both oral doses produced a predominant delivery of estrone to the syst emic circulation. There was no difference in time-averaged LH suppress ion between the three phases. However, estradiol-HPbetaCD sublingually produced greater FSH suppression than oral micronized estradiol.