Minimized estradiol absorption with ultra-low-dose 10 μg 17β-estradiol vaginal tablets

Abstract

Objective To investigate the pharmacokinetics of 10 μg and 25 μg 17β-estradiol (E2) vaginal tablets in postmenopausal women with vaginal atrophy.Methods Fifty-eight women received either 10 μg or 25 μg estradiol vaginal tablets, administered once daily for 2 weeks, followed by twice-weekly dosing for 10 weeks. Blood samples were taken over 24 h at baseline (day -1) and days 1, 14, 82 and 83. Estradiol (E2), estrone (E1) and estrone sulfate (E1S) levels were quantified by gas chromatography–mass spectrometry (GCMS) and assessed by the average plasma concentration from time 0 to 24 h (Cave) derived from the area under the curve within 24 h (AUC(0-24)) divided by 24 h.Results Mean Cave values were 9.39 and 19.84 pg/ml on day 1, 6.56 and 18.29 pg/ml on day 14, and 4.64 and 9.41 pg/ml on day 83 for the 10 μg and 25 μg doses, respectively. After 12 weeks, E1 and E1S levels were slightly higher with the 25 μg dose and in the same range with the 10 μg dose, as compared to baseline.Conclusions During 12 weeks' administration, 10 μg vaginal tablets resulted in at least 50% lower mean estradiol concentrations than with the 25 μg dose within 24 h after dosing. Administering the 25 μg dose, mean E2 levels during the first 2 weeks exceeded the published reference range for postmenopausal women using the GCMS method, while, with the 10 μg dose, mean E2 levels remained in that range from the beginning, indicating minimized estradiol absorption.