Objective: This study aims to demonstrate the bioequivalence (BE) and pharmacokinetic profiles of Apixaban film-coated tablet (Nobel İlaç), a Factor Xa inhibitor, with its reference product Eliquis 5 mg filmtabletten, manufactured by Bristol-Myers Squibb S.r.l., Italy, in healthy male volunteers under fasting conditions. Furthermore, the study design assesses the individual bioequivalence which ensures that a drug is interchangeable between its reference.

Material and Method: We have designed a single-dose, open-label, randomised, cross-over two-period study with a population of 32. The volunteers who have been applied to the study in Farmagen (clinical site) enrolled according to the protocol's criteria by the principal investigator. A validated method using liquid chromatography and tandem mass spectrometry was developed and approved to measure apixaban levels in human plasma. For bioequivalence, Cmax and AUC0-tlast pharmacokinetic parameters were evaluated.

Results: The mean Cmax were 110.474 ng/mL and 114.455 ng/mL; the mean AUC0-tlast were 1130.641 ng.hr/ mL and 1138.439 ng.hr/mL for the test and reference products, subsequently. The comparative geometric mean ratios (90% CI) were 0.9054 - 1.0185 (Cmax) and 0.9560 - 1.0142 (AUC0-tlast). Also, both products were well tolerated, with no significant adverse events reported.

Conclusion: This study showed that both products are bioequivalent under fasting conditions since the key pharmacokinetic parameters of apixaban are found to be within the standard acceptability limits defined (80.00%-125.00%). A crucial study outcome is also the confirmation of individual interchangeability between the products. In conclusion, our BE study leads to an important contribution to pharmacotherapeutic options in anticoagulant therapy by providing a solid evidence base supporting our generic apixaban product with the reference product, Eliquis.

Apixaban Bioequivalence Pharmacokinetics Venous thromboembolism Generic drugs