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.