Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran). Part I. Absolute bioavailability of 0.25 mg of ganirelix after a single subcutaneous injection in healthy female volunteers

Fertil Steril. 1999 Dec;72(6):1001-5. doi: 10.1016/s0015-0282(99)00413-6.

Abstract

Objective: To assess the absolute bioavailability of ganirelix (Antagon/Orgalutran; NV Organon, Oss, the Netherlands) after a single SC injection.

Design: Randomized, crossover, pharmacokinetic study.

Setting: Phase I clinical research unit.

Patient(s): Nineteen healthy female volunteers of reproductive age.

Intervention(s): Two separate injections of 0.25 mg of ganirelix were given, one subcutaneously and one intravenously, with a washout period of 1 week between injections. Blood samples were taken for assessment of serum ganirelix concentrations, and blood pressure, heart rate, and adverse events were monitored.

Main outcome measure(s): Pharmacokinetic parameters.

Result(s): Fifteen subjects were evaluated. The mean concentration-time profile after SC administration was comparable to that after IV administration. The mean (+/- SD) peak concentration and time of occurrence after SC administration were 14.8+/-3.2 ng/mL and 1.1+/-0.3 hours, respectively. The mean (+/- SD) half-lives after IV administration and SC administration were highly similar (12.7+/-3.7 hours and 12.8+/-4.3 hours, respectively). Mean (+/- SD) AUC0-infinity (area under the concentration-time curve) values of 105+/-11 ng/mL x hours and 96+/-12 ng/mL x hours were calculated for IV administration and SC administration, respectively, resulting in an absolute mean (+/- SD) bioavailability of 91.3%+/-6.7%. Both treatments were well tolerated.

Conclusion(s): Ganirelix is absorbed rapidly and extensively after SC administration, resulting in a high absolute bioavailability of >90%.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Availability
  • Cross-Over Studies
  • Female
  • Gonadotropin-Releasing Hormone / adverse effects
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / antagonists & inhibitors*
  • Gonadotropin-Releasing Hormone / pharmacokinetics
  • Gonadotropin-Releasing Hormone / pharmacology
  • Hormone Antagonists / adverse effects
  • Hormone Antagonists / pharmacokinetics
  • Hormone Antagonists / pharmacology*
  • Humans
  • Injections, Intravenous
  • Injections, Subcutaneous
  • Reference Values

Substances

  • Hormone Antagonists
  • Gonadotropin-Releasing Hormone
  • ganirelix