LAUSR

Apatinib, a small molecule anti-angiogenic drug, is proven to be safe and effective for treatment of advanced gastric cancer (AGC). It is also a single drug that significantly prolongs survival after failure of standard chemotherapy for AGC, which has attracted the research interest. The purpose of this study is to evaluate the inhibition effects of apatinib on human and rat cytochrome P450, including CYP3A2/4, CYP2B1/6, CYP2C9/11, CYP2D1/6, and CYP2E1. The IC50 and IC50-shift results indicated that apatinib might not be a time-dependent inhibitor. Apatinib was a weak inhibitor of human CYP2E1 (IC50>10 μM) but inhibited CYP2B6/2B1 and CYP2D6/2D1 in a competitive way (Ki = 3.84/0.59 and 5.41/0.87 μM), and inhibited CYP3A4/3A2 and rat CYP2E1 in a mixed way (Ki = 11.50/1.83 and 13.06 μM). On CYP2C9, apatinb exhibited the noncompetitive inhibition (Ki = 0.71 μM) while it inhibited CYP2C11 uncompetitively (Ki = 3.30 μM).