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

• Published in: Journal of pediatric surgery Vol. 54; no. 7; pp. 1384 - 1390
• Main Authors: Salman, F. Tansu, DiCristina, Cara, Chain, Anne, Afzal, Amna Sadaf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2019
• Subjects: Aprepitant; Pediatric surgery; Pharmacodynamics; Pharmacokinetics; PONV; Postoperative nausea and vomiting; Aprepitant; Pharmacodynamics; PONV; Pharmacokinetics; Pediatric surgery; Postoperative nausea and vomiting
• ISSN: 0022-3468; 1531-5037; 1531-5037
• DOI: 10.1016/j.jpedsurg.2018.09.006

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). 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]). 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. PK, safety, and preliminary efficacy analyses support further clinical evaluation of aprepitant for PONV prophylaxis in pediatric patients. NCT01732458 Therapeutic, Level I.