A Single-Dose Bioequivalence and Food Effect Study With Aprepitant and Fosaprepitant Dimeglumine in Healthy Young Adult Subjects.
Fosaprepitant dimeglumine, a lyophilized prodrug, is rapidly converted to aprepitant, a substance P/neurokinin 1 (NK1 ) receptor antagonist. Intravenous (IV) fosaprepitant and oral aprepitant are used in combination with other antiemetics to prevent chemotherapy-induced nausea and vomiting. This randomized, phase 1 study was designed to assess the aprepitant area under the curve (AUC0-∞ ) equivalence of a single, oral 165-mg or 185-mg dose of aprepitant to a single 150-mg fosaprepitant IV dose infused over 20 minutes, and to evaluate the effect of food on the bioavailability of the oral 165-mg and 185-mg aprepitant doses. Plasma samples were analyzed for aprepitant, and linear mixed-effects models were applied to natural log-transformed aprepitant AUC data. A 2 one-sided tests procedure was used to evaluate bioequivalence; the adjusted P values for the AUC0-∞ of both oral doses versus the IV dose were < .05, supporting the hypothesis that each single, oral dose of aprepitant is equivalent to the AUC0-∞ of a single IV infusion of fosaprepitant. Food effect results suggest that dose adjustment would not be necessary with a single oral dose of aprepitant. Single-dose administration of oral 165 mg and 185 mg aprepitant and IV 150 mg fosaprepitant was generally well tolerated.
Clinical Pharmacology, Merck Sharp & Dohme Corp, North Wales, PA, USAEarly Development Statistics, Merck Sharp & Dohme Corp, North Wales, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme Corp, West Point, PA, USABuffalo Clinical Research Center LLC, Buffalo, NY, USA.
Craig R
CR
Shadle
Clinical Pharmacology, Merck Sharp & Dohme Corp, North Wales, PA, USAEarly Development Statistics, Merck Sharp & Dohme Corp, North Wales, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme Corp, West Point, PA, USABuffalo Clinical Research Center LLC, Buffalo, NY, USA.
M Gail
MG
Murphy
Clinical Pharmacology, Merck Sharp & Dohme Corp, North Wales, PA, USAEarly Development Statistics, Merck Sharp & Dohme Corp, North Wales, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme Corp, West Point, PA, USABuffalo Clinical Research Center LLC, Buffalo, NY, USA.
Yang
Y
Liu
Clinical Pharmacology, Merck Sharp & Dohme Corp, North Wales, PA, USAEarly Development Statistics, Merck Sharp & Dohme Corp, North Wales, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme Corp, West Point, PA, USABuffalo Clinical Research Center LLC, Buffalo, NY, USA.
Maureen
M
Ho
Clinical Pharmacology, Merck Sharp & Dohme Corp, North Wales, PA, USAEarly Development Statistics, Merck Sharp & Dohme Corp, North Wales, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme Corp, West Point, PA, USABuffalo Clinical Research Center LLC, Buffalo, NY, USA.
Daniel
D
Tatosian
Clinical Pharmacology, Merck Sharp & Dohme Corp, North Wales, PA, USAEarly Development Statistics, Merck Sharp & Dohme Corp, North Wales, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme Corp, West Point, PA, USABuffalo Clinical Research Center LLC, Buffalo, NY, USA.
Susie Xiujiang
SX
Li
Clinical Pharmacology, Merck Sharp & Dohme Corp, North Wales, PA, USAEarly Development Statistics, Merck Sharp & Dohme Corp, North Wales, PA, USAPharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck Sharp & Dohme Corp, West Point, PA, USABuffalo Clinical Research Center LLC, Buffalo, NY, USA.
Robert A
RA
Blum
aprepitant; bioequivalence; food effect; fosaprepitant; tolerability