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 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-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

Acknowledgements

The authors would like to acknowledge Jolene Mason, PhD and Laura Ninger, ELS of Precise Publications, LLC for their assistance in the writing of this manuscript.

Conflict of interest

Dr Pickar was formerly an employee of Wyeth Research; has received consultant fees from Wyeth/Pfizer, Besins Healthcare, Shionogi Inc., Metagenics, Radius Health, Inc, and TherapeuticsMD; and has stock options with TherapeuticsMD. Dr Bernick, Dr Mirkin, and Ms Amadio are employees of TherapeuticsMD.

Source of funding

TherapeuticsMD sponsored the study and funded the medical writing support provided by Jolene Mason, PhD and Laura Ninger, ELS of Precise Publications, LLC.