Application of liquid chromatography–tandem mass spectrometry to study the effect of docetaxel on pharmacokinetics and tissue distribution of apatinib in mice
2018
Feng, Siqi | Zhang, Jingwei | Wang, Ying | Sun, Runbin | Feng, Dong | Peng, Ying | Yang, Ne | Zhang, Yue | Gao, Haoxue | Gu, Huilin | Wang, Guangji | Aa, Jiye | Zhou, Fang
Apatinib, a highly selective small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), has attracted many attentions due to its anticancer activity in various malignancies containing non-small-cell lung cancer (NSCLC). Our previous preclinical study confirmed the enhanced anti-tumor efficacy of combined treatment between apatinib and docetaxel for NSCLC. However, the effects of docetaxel on pharmacokinetics and tissue distribution of apatinib are not clear. In present study, a reliable HPLC-MS/MS method was established for determination of apatinib. This method had a good linearity in the range of 1–5000 ng/mL, and the recovery and matrix effect were 100.1–103.5%, 77.6–83.5%, respectively. Plasma exposure level of apatinib and the values of Cmax, AUC0–12h, T1/2, and MRT were not affected by multi-dose of docetaxel. The tissue distributions (kidney, heart, lung, spleen) of apatinib in combined treatment group were lower at 0.25 h but higher at 2 h, and that in intestine and liver were not significantly changed compared with control group. However, pre-treatment with docetaxel had no significant effect on AUC0–4h of apatinib in tissues in mice. In conclusion, plasma and tissues exposure levels of apatinib were not affected by long-termed treatment with docetaxel, indicating that docetaxel is less likely to increase the side effect of apatinib such as hypertension, hand-foot syndrome and so on.
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