Figure legand
Figure.
1. CYP-dependent oxidation of rivaroxaban to hydroxylated rivaroxaban.
Figure. 2. (A) HPLC profile of rivaroxaban and metabolite M1 in
the presence or absence of NADPH. (B) Total ion chromatograms of
metabolite M1.
Figure. 3. M1 formation catalyzed by various recombinant human
CYPs. Rivaroxaban (120 μM) was incubated with human CYPs (0.4
mg·mL−1) at 37 °C for 60 minutes. Results are shown as
the mean ± S.D. of at least three determinations performed in duplicate.
N.D.: Not detectable.
Figure. 4 . Kinetic plots of rivaroxaban metabolism after
incubation with (A) HLM; (B) CYP2D6, CYP2J2, CYP3A4 and CYP4F3. Inset:
Eadie-Hofstee transformation.
Figure. 5 . The effect of P450-specific inhibitors on
rivaroxaban hydroxylation in HLM. The data are shown as mean ± S.D. from
three independent experiments performed in duplicate.*P < 0.05 and**P < 0.01 vs the control group; ns:
not significant (P > 0.05 vs the control group).
Figure. 6 . (A) Conformation of rivaroxaban with the iron in
porphyrin ring of CYP2J2 and (B) corresponding 2D molecular interaction
diagram.