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

Abstract

Objective: To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17β-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.

Keywords: Bioavailability; estradiol; menopause; pharmacokinetics; vaginal estrogen therapy; vulvar and vaginal atrophy.

Figure 1.

Linear plot of baseline-corrected mean plasma concentration versus time for (a) estradiol (n = 34), (b) estrone (n = 33), and (c) estrone sulfate (n = 24) after treatment with the test and reference preparations, each at 10 μg. Test product: TX-004HR; TherapeuticsMD, Inc., Boca Raton, FL. Reference product: Vagifem®; Novo Nordisk, Plainsboro, NJ.

Figure 2.

Linear plot of baseline-corrected mean plasma concentration versus time for (a) estradiol (n = 36), (b) estrone (n = 36), and (c) estrone sulfate (n = 36) after treatment with the test and reference preparations, each at 25 μg. Test product: TX-004HR; TherapeuticsMD, Inc., Boca Raton, FL. Reference product: Vagifem®; Novo Nordisk, Plainsboro, NJ.