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

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) AUC 0–∞ (area under the concentration-time curve) values of 105 ± 11 ng/mL × hours and 96 ± 12 ng/mL × 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%.