Pharmacokinetics and pharmacodynamics of aprepitant for the prevention of postoperative nausea and vomiting in pediatric subjects.

BACKGROUND/PURPOSE: This multicenter, randomized, partially-blinded phase IIb study evaluated the pharmacokinetics (PK)/pharmacodynamics, safety, and tolerability of aprepitant in pediatric subjects for the prevention of postoperative nausea and vomiting (PONV). METHODS: Subjects aged birth to 17 years scheduled to undergo surgery and receive general anesthesia with ≥1 risk factor for PONV were randomly assigned to 1 of 3 aprepitant dose regimens (a single oral dose of aprepitant equivalent to adult doses of 10 mg, 40 mg, or 125 mg), or a control regimen of ondansetron before anesthesia. Assessments included PK, safety, and exploratory efficacy (complete response [CR; no emesis, retching, or dry heaves and no rescue therapy within 0-24 h following surgery] and no vomiting [NV; no emesis, retching, or dry heaves within 0-24 h following surgery]). RESULTS: Of 220 randomized and treated subjects, 119 receiving a single aprepitant dose were sampled for PK analysis and had evaluable aprepitant plasma concentrations. A dose-dependent relationship in exposure (AUC0-8 h and Cmax) was observed. Aprepitant was generally well tolerated, and the CR and NV rates were high (>80%) across treatment groups. CONCLUSIONS: PK, safety, and preliminary efficacy analyses support further clinical evaluation of aprepitant for PONV prophylaxis in pediatric patients. CLINICALTRIALS. GOV ID: NCT01732458 LEVEL OF EVIDENCE: Therapeutic, Level I.