Pharmacokinetics and Bioequivalence of Two Formulations of Apixaban Tablets: A Double-Blind, Single-Dose, Crossover Study in Healthy Subjects

Abstract

Background: The present study aimed to determine the pharmacokinetic parameters and bioequivalence of the test medicinal product, apixaban 5 mg tablet, and its reference product, Eliquis®, in healthy male and female subjects under a fasted state. Methods: Before in vivo evaluation, the quality control parameters of the products were evaluated and compared. This study was a single-dose, double-blind, 2-sequence, crossover, 2-period, randomized bioequivalence and pharmacokinetic study in 24 healthy individuals with a two-week washout period between doses. A series of blood samples were obtained over 48 hours after dose administration, and the samples were analyzed for their apixaban content using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique. The pharmacokinetic parameters were computed using non-compartmental analysis. Results: Both products passed the in vitro quality control criteria. Following administration of the apixaban tablet, the area under curve (AUC)0-t, AUC0-∞, and maximum plasma concentration (Cmax) mean values for the test product were 1284.0 ng.h/mL, 1368.2 ng.h/mL, and 157.4 ng/mL, respectively, and for the reference product were 1310.6 ng.h/mL, 1406.5 ng.h/mL, and 157.6 ng/mL, respectively. The 90% confidence intervals (CI) of the geometric mean ratio for AUC0-t (91.4 - 105.9), AUC0-∞ (92.9 - 106.9), and Cmax (87.1 - 101.9) fell within the predefined accepted range of 80% - 125%. No serious adverse events were observed. Conclusions: The test product (apixaban 5 mg tablet) and reference product (Eliquis®) achieved regulatory requirements for bioequivalence in healthy individuals under a fasted state.