A Single-Dose Pharmacokinetic and Bioequivalence Study of Generic and Original Aprepitant in Healthy Volunteers

Abstract

Introduction. Chemotherapy-induced nausea and vomiting may lead to dehydration, malnutrition, and electrolyte imbalances, subsequently resulting in prolonged hospitalization and treatment refusal by patients. The addition of aprepitant to chemotherapy regimens in adult patients has demonstrated high efficacy in reducing emetogenic potential.

Aim. To compare the pharmacokinetic profile and establish bioequivalence, safety, and tolerability of the test (T) and reference (R) aprepitant in healthy volunteers following a single oral dose on an empty stomach.

Materials and Methods. A prospective, open-label, randomized, crossover study of comparative pharmacokinetics and bioequivalence of T and R drugs (125 mg) administered as a single oral dose to healthy adult volunteers of both sexes under fasting conditions. Blood plasma samples were collected to determine aprepitant concentrations. Pharmacokinetic and statistical analyses were performed, and 90 % confidence intervals (CI) were calculated for the ratio of geometric means of key pharmacokinetic variables: C_max, t_max, AUC_0-t, AUC_0–∞, AUC_t-∞, t_1/2 and AUC_t-∞/AUC_0-∞.

Results. Pharmacokinetic data from 36 patients established bioequivalence between T and R drugs. The 90 % CIs for the ratio of AUC_0-t and C_max values for aprepitant were 89.25–107.81 % (mean ratio 98.09 %) and 85.84–106.32 % (mean ratio 95.54 %), respectively, falling within the accepted bioequivalence range of 80–125 %. Safety analysis indicated that both formulations were well tolerated. No statistically significant differences were observed in vital signs, instrumental findings, or laboratory parameters throughout the study compared to baseline values. Furthermore, no significant differences in adverse events were observed between the two formulations.

Conclusion. This study establishes the bioequivalence of the test and reference aprepitant formulations. Additionally, the data indicate comparable safety profiles between the two products.