Bioequivalence study of two formulations of rivaroxaban in healthy adult subjects under fasting conditions

Abstract

Objectives: Oral anticoagulants exert their antithrombotic effect by disrupting the coagulation cascade. Rivaroxaban is the first oral agent to be developed that inhibits the coagulation process by binding directly to Factor Xa in a competitive manner. The aim of this study was to demonstrate the bioequivalence (BE) and safety of a generic formulation of rivaroxaban by comparing their pharmacokinetic (PK) parameters through statistical data and criteria of validation. Oral tablet formulations of 20 mg of a commercial product rivaroxaban reference (R) were tested against a generic product test (T) in 24 healthy adults under fasting condition. Materials and Methods: The study was an open label, balanced, randomized, two-treatment, two-period, two-sequence, single oral dose, and crossover study. Blood samples were collected pre-dose and at specified intervals up to 48-h post-dose to evaluate PK parameters by quantifying the concentration of rivaroxaban in plasma using a validated Liquid chromatography-mass spectrometry (LC-MS/MS) method of analysis. Statistics and confidence intervals (CIs) were calculated for BE purposes. Results: The geometric means of the T/R ratios and 90% confidence intervals (CIs) were: Cmax 87.80% (82.74 –93.12%), AUC0-t 85.96% (81.88–90.24%), and AUC0-∞ 86.13% (82.2–90.35%). All PK parameters are within BE acceptance range of 80–125% for demonstration of average bioequivalence. Conclusions: The study demonstrates the BE and well tolerance of both formulations of rivaroxaban in healthy subjects under fasting conditions.