Specific chemical inhibitor study
To identify the enzymes involved in metabolism, several CYP-specific inhibitors were added to the incubation with rivaroxaban (120 μM). The inhibitor concentrations were as follows: 8-mthoxypsoralen (2.5 μM) for CYP2A6, montelukast (5 μM) for CYP2C8, sulfaphenazole (10 μM) for CYP2C9, quinidine (10 μM) for CYP2D6, danazol (3 μM) for CYP2J2 and ketoconazole (1 μM) for the CYP3A subfamily [19-21]. The 120 μM rivaroxaban concentration was selected based on theK m value. The final concentration of organic solvent in the incubation media was no more than 0.5% (v/v). Results were from at least three experiments carried out in duplicate.