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

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), AUC, and maximum plasma concentration (C) 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 AUC (91.4 - 105.9), AUC (92.9 - 106.9), and C (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.