RESUMEN
OBJECTIVE: To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17ß-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®, reference) in postmenopausal women (aged 40-65 years) at 10-µg and 25-µg 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-µg study and 36 completed the 25-µg 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 AUC0-24 and Cmax and earlier tmax. 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-µg and 25-µg doses. Both doses of each product were safe and well-tolerated.