DMD Highlight: Application of Static Modeling in the Prediction of In Vivo Drug–Drug Interactions between Rivaroxaban and Antiarrhythmic Agents
Rivaroxaban, a direct Factor Xa inhibitor, is indicated for stroke prevention in nonvalvular atrial fibrillation (AF) and amiodarone and dronedarone are antiarrhythmic agents employed in AF management. In vitro assays using rivaroxaban as the probe substrate were used to study inhibition of CYP3A4 and 2J2 by amiodarone, dronedarone and their metabolites. The inhibition parameters were fitted into a mechanistic static model, which predicted a 37% and 31% increase in rivaroxaban exposure due to the inhibition of hepatic and gut metabolism by amiodarone and dronedarone, respectively.
See the article by Cheong et al. at Drug Metabolism and Disposition March 2017, 45 (3) 260-268; DOI: https://doi.org/10.1124/dmd.116.073890