Inhibition Mechanism of Ketamine-Apatinib by CYP2C9 and 3A4: A Prediction of Possible Drug-Drug Interaction.
Biopharmaceutics & drug disposition May 21, 2025 Xiang Zheng, Haiyan Chen, Dan Lin et al. 2 citations
Apatinib, a VEGFR2 inhibitor used for gastric cancer, inhibits the metabolism of the pain-relief drug ketamine by interacting with cytochrome P450 enzymes. In laboratory assays, apatinib acted as a noncompetitive inhibitor of CYP2C9*1, CYP2C9*16, and rat liver microsomes; a competitive inhibitor of CYP2C9*3 and CYP2C9*13; and a mixed-model inhibitor of four CYP3A4 alleles. Molecular docking showed apatinib binds more strongly to CYP3A4*1 than ketamine does. Co-administration may increase adverse effects in poor metabolizers, and in vivo studies are needed to confirm this interaction.