Pharmacokinetics and Safety of Estradiol Valerate Tablet and Its Generic: A Phase 1 Bioequivalence Study in Healthy Chinese Postmenopausal Female Subjects

Drug Des Devel Ther. 2024 Jul 10:18:2891-2904. doi: 10.2147/DDDT.S460681. eCollection 2024.

Abstract

Purpose: Estradiol valerate (Progynova®) is used as hormone therapy to supplement estrogen deficiency. This study aimed to assess the bioequivalence of an estradiol valerate tablet and its generic form, under fasting and fed conditions.

Methods: A randomized, open-label, single-dose, 2-period crossover study was conducted on healthy postmenopausal Chinese female volunteers under fasting and fed conditions. For each period, the subjects received either a 1 mg tablet of estradiol valerate or its generic. Blood samples were collected before dosing and up to 72 hours after administration. Plasma levels of total estrone, estradiol, and unconjugated estrone were quantified using a validated liquid chromatography-tandem mass spectrometry method.

Results: A total of 54 volunteers were enrolled in this study. The primary pharmacokinetic parameters, including Cmax, AUC0-t, and AUC0-∞, were similar for the two drugs under both fasting and fed conditions, with 90% confidence intervals for the geometric mean ratios of these parameters, all meeting the bioequivalence criterion of 80-125%. A total of 48 adverse events (AEs) were reported in the fed study compared with 24 AEs in the fasting study.

Conclusion: Estradiol valerate and its generic form were bioequivalent and well tolerated under both fasting and fed conditions.

Keywords: bioequivalence; estradiol valerate; pharmacokinetics; postmenopausal; safety.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • China
  • Cross-Over Studies
  • Drugs, Generic* / administration & dosage
  • Drugs, Generic* / adverse effects
  • Drugs, Generic* / pharmacokinetics
  • East Asian People
  • Estradiol* / administration & dosage
  • Estradiol* / analogs & derivatives
  • Estradiol* / blood
  • Estradiol* / pharmacokinetics
  • Female
  • Healthy Volunteers
  • Humans
  • Middle Aged
  • Postmenopause*
  • Tablets
  • Therapeutic Equivalency

Substances

  • Drugs, Generic
  • Estradiol
  • Tablets

Grants and funding

This study was supported by Zhejiang XianJu Pharmaceutical Co., Ltd., the Science and Technology Research Project of Sichuan Provincial Administration of Traditional Chinese Medicine (2021MS198), and the Incubation Project of Deyang People’s Hospital (FHS202204). The funder was not involved in the study design, data collection, analysis, interpretation, article writing, or the decision to submit the manuscript for publication.