Apixaban Pharmacokinetics and Bioequivalence of Two Tablet Formulations: A Randomized, Open‐Label, Crossover Study, Fasting Condition in Healthy Indonesian Volunteers

Abstract

AbstractThe present study aimed to assess the bioequivalence of a new apixaban generic with reference formulation. Twenty‐six healthy volunteers were recruited for an open‐label, balanced, randomized, 2‐treatment, 2‐sequence, 2‐period, single oral dose study. Following overnight fasting, each volunteer received 5 mg of apixaban test and reference formulations as single doses, separated by a 1‐week washout period. Twenty blood samples were collected at predose and multiple time points between 0.5 and 72 hours after dosing. A validated ultra‐performance liquid chromatography‐tandem mass spectrometry detection method following a protein precipitation step was implemented to determine apixaban concentrations. Noncompartmental analysis was used to derive the pharmacokinetic parameters, which were then compared between the test and reference products using a multivariate analysis of variance. The pharmacokinetic parameters of the test product were not statistically different from the reference product, and the 90% confidence intervals of apixaban natural log‐transformed area under the concentration‐time curve from time 0 to infinity, area under the concentration‐time curve from time 0 to the last measurable concentration, and maximum concentration were within 80%‐125% based on the bioequivalence acceptance range criteria. The test and reference formulations of apixaban are bioequivalent in healthy subjects under fasting conditions.