Pharmacokinetic and pharmacodynamic evaluation of the new prolonged-release leuprorelin acetate microspheres for injection compared with Enantone® in healthy Chinese male volunteers

Expert Opin Drug Metab Toxicol. 2021 Sep;17(9):1149-1156. doi: 10.1080/17425255.2021.1948534. Epub 2021 Aug 10.

Abstract

Purpose: To compare the pharmacokinetics, pharmacodynamics and safety of the new prolonged-release leuprorelin acetate microspheres for injection (3.75 mg) with the reference product Enantone® (3.75 mg).

Method: 48 healthy male volunteers were enrolled and randomly received a single 3.75 mg dose of the test drug or Enantone®.

Results: There were no significant differences in Cmax, AUC0-t and AUC0-48 between the test group and reference group (P > 0.05). The 90% confidence intervals of the two groups were 87.49%~112.74%, 97.15%~154.25%, and 80.85%~109.01%, respectively. Twenty-eight days after administration, both groups reached 100.0% castration level; there was no difference in the time from administration to reaching castration level between the two groups (P > 0.05); However, the difference between the two groups in the duration of castration level was statistically significant (P < 0.05). There were no major or serious adverse events, and the severity was mild to moderate.

Conclusion: The pharmacokinetic characteristics of leuprorelin in two groups were consistent. The two groups exhibited similar inhibitory effects on testosterone and more subjects in the test group maintained a longer castration time than those in the reference group.

Keywords: Enantone®; New prolonged-release leuprorelin acetate microspheres for injection; PK; castration; safety; testosterone.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antineoplastic Agents, Hormonal / administration & dosage*
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Antineoplastic Agents, Hormonal / pharmacology
  • Area Under Curve
  • Delayed-Action Preparations
  • Humans
  • Injections
  • Leuprolide / administration & dosage*
  • Leuprolide / pharmacokinetics
  • Leuprolide / pharmacology
  • Male
  • Microspheres
  • Single-Blind Method
  • Testosterone / blood*
  • Time Factors
  • Young Adult

Substances

  • Antineoplastic Agents, Hormonal
  • Delayed-Action Preparations
  • Testosterone
  • Leuprolide