Kinetic analysis
Rivaroxaban (1−100 μM) was incubated with pooled HLM (0.3 mg protein·mL−1) for 60 min to evaluate the kinetic parameters of the HLM. Rivaroxaban (1−200 μM for CYP2J2, 10−200 μM for CYP 2D6 and 20−200 μM for CYP4F3) was incubated with recombinant CYPs (0.4 mg protein·mL−1) for 60 min to determine the kinetic parameters of the recombinant CYPs. The incubation conditions were as described above. The apparent K m andV max values were calculated from nonlinear regression analysis of experimental data according to the Michaelis-Menten equation with GraphPad Prism, version 7. All incubations were carried out in three independent experiments performed in duplicate.