CYP screening
Screening experiments with the 17 recombinant enzymes revealed CYP2D6, CYP2J2, CYP3A4 and CYP4F3 to be the four major CYPs for rivaroxaban hydroxylation, as shown by M1 peak area (24.1, 391.6, 25.0 and 14.9), respectively; Figure 3). CYP1A1, CYP3A5 and CYP3A7 also participated in rivaroxaban hydroxylation, but to a lesser extent; however, CYPs 1A2, 1B1, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 4F2 and 46A1 were essentially inactive. The catalytic activity of the various CYPs was in the following order: 2J2 > 3A4 > 2D6 > 4F3 > 1A1 > 3A5 > 3A7 > 2A6 > 2E1 > 2C9 > 2C19. Notably, CYP2J2 showed the strongest catalytic activity in rivaroxaban hydroxylation of the 17 CYPs, which was approximately 16-, 16- and 26-fold higher than that of CYP2D6, CYP3A4 and CYP4F3, respectively.