Bioequivalence Analysis of Ondansetron Hydrochloride Tablets in Healthy Chinese Subjects: A Randomized, Open-Label, Two-Period Crossover Phase I Study.

Abstract

Ondansetron is a highly selective 5-HT3 receptor antagonist that alleviates nausea and vomiting. Bioequivalence evaluation ensures that the efficacy of generic drugs is consistent with that of the original drug. The objective of this study was to evaluate the bioequivalence of ondansetron hydrochloride (HCl) tablets taken in single doses under fasting and postprandial conditions in healthy subjects. In this randomized, open-label, two-cycle, crossover phase I study, liquid chromatography‒tandem mass spectrometry (LC‒MS/MS) was used to determine the ondansetron concentration in dipotassium-ethylenediaminetetraacetate (K2-EDTA) plasma after the subjects received a single 8 mg of ondansetron and reference formulation. Twenty-six healthy subjects received one tablet of ondansetron under fasting conditions and 28 subjects received one under postprandial conditions. Bioequivalence was established if the 90% confidence interval (CI) was 80.00-125.00%. The pharmacokinetic parameters were calculated via WinNonLin 8.1 software and the bioequivalence data were evaluated via Phoenix WinNonlin 8.1 statistics software. The geometric mean ratio (GMR) of the maximum observed concentration (Cmax), the area under the plasma concentration‒time curve (AUC) from time zero to the last sampling time (AUC0-t), and the AUC from time zero to infinity (AUC0-∞) from the test/reference formulation under fasting conditions were 90.50, 90.43, and 90.25, respectively. The 90% CIs were 83.75-97.79, 82.64-98.95, and 82.25-99.03, respectively. The GMRs of Cmax, AUC0-t, and AUC0-∞ after a high-fat meal were 96.85, 93.57, and 93.77, respectively; the 90% CIs were 88.43-106.07, 87.35-100.24, and 87.35-100.68, respectively. The test and reference formulations of ondansetron HCl have bioequivalence for healthy adult subjects under fasting and postprandial conditions.