title: 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.
  
  
  CONCLUSIONS
  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.
authors: a Columbia University Medical Center , New York , NY , USA ;
authors: J H
authors: JH
authors: Pickar
authors: b TherapeuticsMD , Boca Raton , FL , USA.
authors: J M
authors: JM
authors: Amadio
authors: b TherapeuticsMD , Boca Raton , FL , USA.
authors: B A
authors: BA
authors: Bernick
authors: b TherapeuticsMD , Boca Raton , FL , USA.
authors: S
authors: S
authors: Mirkin
mesh_terms: D000282:Administration, Intravaginal; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D018592:Cross-Over Studies; D004958:Estradiol / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D012995:Solubility; D013607:Tablets
chemical_list: D002214:Capsules; D013607:Tablets; D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate
keywords: Bioavailability; estradiol; menopause; pharmacokinetics; vaginal estrogen therapy; vulvar and vaginal atrophy