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.