Conclusion
In summary, all three TKIs (imatinib, sunitinib and gefitinib) showed
inhibitory effects on CYP2J2- and CYP3A4-mediated rivaroxaban
metabolism. Imatinib and gefitinib exerted significant reversible
inhibition of CYP2J2 and CYP3A4, while sunitinib only showed reversible
inhibition of CYP3A4. The three TKIs also demonstrated time-dependent
inactivation of CYP3A4, with this effect being slight on CYP2J2.
Furthermore, the combination of rivaroxaban with imatinib was predicted
to constitute a moderate DDI risk. Our results provide data for the
clinical safety assessment of the combination of rivaroxaban with
imatinib, sunitinib and gefitinib in cancer patients, and also give new
insights for DDI assessment involving rivaroxaban.