Apatinib, a small molecule anti-angiogenic tyrosine kinase inhibitor is used extensively to treat advanced gastric cancer and simvastatin (SV) is often co-prescribed to treat cardiovascular disease in cancer patients. As both apatinib and SV are metabolized primarily by cytochrome P450 variant CYP3A4, they are likely to interact. Therefore, the potential effect of SV co-administration on pharmacokinetics of apatinib in Sprague-Dawley male rats is demonstrated for the first time.

Sixteen rats were randomly divided into two groups (n = 8), 2 mg/kg SV orally co-administrated for seven days (group B) and the corresponding control group (group A). Apatinib concentrations of rat plasma samples were detected by ultra-performance liquid chromatography tandem mass spectrometry. Pharmacokinetic parameters were calculated using non compartmental methods.

Co-administration of SV for seven days significantly increased area under curve (AUC_(0-t)), AUC_(0-∞) and maximum plasma concentration of apatinib by 2.4-, 2.4-, and 2.7-fold, respectively while decreasing apparent volume of distribution and clearance by 81.7 and 73.9%, respectively.

These findings suggest that concomitant administration of SV with 7 days may have inhibited the metabolism of apatinib in rats.

阿帕替尼是一种小分子抗血管生成酪氨酸激酶抑制剂，已广泛用于治疗晚期胃癌，而辛伐他汀（SV）通常被共同处方用于治疗癌症患者的心血管疾病。由于apatinib和SV均主要通过细胞色素P450变异体CYP3A4代谢，因此它们可能相互作用。因此，首次证明了SV共同给药对Sprague-Dawley雄性大鼠中apatinib药代动力学的潜在影响。

将16只大鼠随机分为两组（n  = 8），分别口服2 mg / kg SV连续7天（B组）和相应的对照组（A组）。通过超高效液相色谱串联质谱法检测阿帕替尼浓度的大鼠血浆样品。使用非分隔方法计算药代动力学参数。

SV共同给药7天显着增加曲线下面积（AUC _（0-t）），AUC _（0-∞）和阿帕替尼的最大血浆浓度分别为2.4倍，2.4倍和2.7倍，同时降低明显发行量和清盘量分别减少了81.7％和73.9％。

这些发现表明，与SV同时给药7天可能抑制了大鼠阿帕替尼的代谢。