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

Objective: To assess the absolute bioavailability of ganirelix (Antagon/Org alutran; NV Organon, Oss, the Netherlands) after a single SC injection. Design: Randomized, crossover, pharmacokinetic study. Setting: Phase I clin ical 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 ganir elix concentrations, and blood pressure, heart rate, and adverse events wer e monitored. Main Outcome Measure(s): Pharmacokinetic parameters. Result(s): Fifteen subjects were evaluated. The mean concentration-time pro file after SC administration was comparable to that after IV administration . The mean (+/-SD) peak concentration and time of occurrence after SC admin istration 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 hig hly similar (12.7 +/- 3.7 hours and 12.8 +/- 4.3 hours, respectively). Mean (CSD) AUG(0-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 absolu te mean (+/- SD) bioavailability of 91.3% +/- 6.7%. Both treatments were we ll tolerated. Conclusion(s): Ganirelix is absorbed rapidly and extensively after SC admin istration, resulting in a high absolute bioavailability of >90%. ((C)1999 b y American Society for Reproductive Medicine.).