Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule

Objective To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17 beta-estradiol for vulvar and vaginal atrophy and compare its pharmacokinetics with that of an approved vaginal estradiol tablet in healthy postmenopausal women. Methods Two randomized, single-dose, two-way cross-over, relative bioavailability trials compared the pharmacokinetics of a solubilized vaginal estradiol softgel capsule (TX-004HR, test) with that of a vaginal estradiol tablet (Vagifem (R), reference) in postmenopausal women (aged 40-65 years) at 10-mu g and 25-mu g doses. In each study, women were randomly assigned to receive a single dose of the test capsule or reference tablet, followed by a single dose of the alternate drug after a 14-day washout. Results Thirty-five women completed the 10-mu g study and 36 completed the 25-mu g study. Significantly lower systemic levels of estradiol, estrone, and estrone sulfate at both doses of the test product were observed compared with equivalent doses of the reference product, with lower AUC(0-24) and C-max and earlier t(max). No adverse events were reported in either trial. Conclusion TX-004HR, a novel estradiol vaginal softgel capsule, exhibited significantly lower systemic exposure than equivalent doses of an approved vaginal estradiol tablet at both 10-mu g and 25-mu g doses. Both doses of each product were safe and well-tolerated.