Pharmacokinetics of a Single 150‐mg Intravenous Infusion of Fosaprepitant: Effects of Concentration and Infusion Time in Healthy Japanese Men

Purpose Fosaprepitant dimeglumine (Proemend® for Injection; formerly ONO‐7847) is a phosphorylated prodrug that is rapidly converted to aprepitant, an oral selective neurokinin‐1 receptor antagonist approved for the prevention of chemotherapy‐induced nausea and vomiting. This Phase 1 study evaluated the pharmacokinetics, safety, and tolerability of fosaprepitant after a single intravenous dose in healthy Japanese men. Methods All fosaprepitant‐ or placebo‐treated subjects were assessed for the occurrence of adverse events. Results Ninety subjects were randomized into treatment and placebo groups. The plasma fosaprepitant concentrations generally reached steady state by 15 minutes after the start of infusion. Although the maximum concentration was proportional to the infusion time, no clinically important pharmacokinetic differences were noted in the cohorts examined. Most adverse events observed in this study were associated with infusion site reactions, which tended toward a higher incidence with shorter infusion times. These events were mild in severity. Conclusions These findings demonstrate that fosaprepitant at different concentrations and over different infusion times has a pharmacokinetic and safety profile that is comparable to the intravenous dose previously established as efficacious and well tolerated. The dosing flexibility afforded by the single‐dose fosaprepitant formulation should lead to greater convenience for patients and health care providers.