TX-004HR vaginal estradiol has negligible to very low systemic absorption of estradiol.
Level 2 - randomized trial
Pharmacokinetic substudy of a randomized, double-blind, placebo-controlled trial
PubMed 28002201 · doi:10.1097/GME.0000000000000790
What was done
A pharmacokinetic substudy of the multicenter, double-blind, placebo-controlled Phase 3 REJOICE trial evaluated TX-004HR vaginal estradiol softgel capsules in 72 postmenopausal women (mean age 59 years) with moderate-to-severe dyspareunia and vulvar and vaginal atrophy. Participants received daily doses of 4, 10, or 25 μg TX-004HR or placebo for 2 weeks, followed by twice-weekly dosing for 10 weeks. Serum was collected at 2, 4, 6, 10, and 24 hours post-dose on days 1 and 14, and once on day 84, to analyze area under the curve, tmax, Cmin, Cavg, and Cmax for estradiol, estrone, and estrone conjugates.
What was found
The 4 μg dose showed no statistically significant differences from placebo in estradiol pharmacokinetic parameters. At 10 μg, estradiol Cmax was statistically higher than placebo on day 1, but did not differ from placebo on day 14. With 25 μg, estradiol pharmacokinetic parameters were statistically higher than placebo, with estradiol Cavg of 9.1 pg/mL on day 1 and 7.1 pg/mL on day 14. Estrone and estrone conjugate parameters were lower than or similar to placebo across all doses, with no drug accumulation observed.
Why it matters
These findings show that ultra-low and low-dose vaginal estradiol (4 μg and 10 μg) provide local delivery with negligible systemic absorption that remains comparable to placebo levels after 14 days.
Limits
The sample size for this pharmacokinetic substudy was relatively small (72 women distributed across four arms). The abstract reports mean Cavg values only for the 25 μg dose and lacks confidence intervals, exact p-values, and long-term systemic clinical safety endpoints.
Cited by
- context Intravaginally administered medications such as estradiol are rapidly absorbed through vaginal tissue and can be measured in the bloodstream within minutes.