Pharmacokinetic and pharmacodynamic characteristics of ganirelix (Antagon/Orgalutran∗∗Orgalutran, NV Organon, Oss, the Netherlands.). part II. dose-proportionality and gonadotropin suppression after multiple doses of ganirelix in healthy female volunteers

摘要: Abstract Objective: To assess the dose-proportionality and pharmacodynamic properties of multiple doses ganirelix (Antagon/Orgalutran; NV Organon, Oss, Netherlands). Design: Randomized, parallel, pharmacokinetic, study. Setting: Phase I clinical research unit. Patient(s): Three groups 15 healthy female volunteers reproductive age. Intervention(s): Subcutaneous injections 0.125 mg, 0.25 or 0.50 mg were given once daily for 7 days. Blood samples taken to serum ganirelix, LH, FSH, E 2 concentrations. Main Outcome Measure(s): Pharmacokinetic parameters hormone suppression. Result(s): Steady-state levels reached between days 3. Peak concentrations, which occurred approximately 1 hour after dosing, increased in a dose-proportional manner averaged 5.2 ng/mL, 11.2 22.2 ng/mL 0.125-mg, 0.25-mg, 0.50-mg doses, respectively. Corresponding mean values area under curve over one dosing interval (24 hours) 33 ng · h/mL, 77.1 137.8 After last 0.25-mg dose concentrations maximally decreased (by 74%, 32%, 25% at 4 hours, 16 hours injection, respectively). Serum returned pretreatment within injection. Conclusion(s): The pharmacokinetics range studied. Multiple resulted immediate suppression gonadotropins, was rapidly reversed treatment discontinuation.