1. Pharmacokinetics and pharmacodynamics of aprepitant for the prevention of postoperative nausea and vomiting in pediatric subjects.
- Author
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Salman FT, DiCristina C, Chain A, and Afzal AS
- Subjects
- Adolescent, Antiemetics pharmacology, Antiemetics therapeutic use, Aprepitant pharmacology, Aprepitant therapeutic use, Child, Child, Preschool, Double-Blind Method, Female, Humans, Infant, Infant, Newborn, Male, Postoperative Nausea and Vomiting drug therapy, Treatment Outcome, Antiemetics pharmacokinetics, Aprepitant pharmacokinetics, Postoperative Nausea and Vomiting prevention & control
- Abstract
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., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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