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.