兰索拉唑对卡博替尼在大鼠体内药动学的影响

目的：具研究兰索拉唑对卡博替尼在大鼠体内药动学的影响。方法：将16只大鼠随机分2组，分别给予生理盐水和兰索拉唑8 mg·kg^-1·d^-1，连续5 d，第6天分别对2组大鼠灌胃给予卡博替尼（1.5 mg·kg^-1），并于给药后不同时间点采集血样，采用高效液相色谱-串联质谱（HPLC-MS/MS）法测定血浆中卡博替尼的含量，计算药动学参数，研究兰索拉唑对卡博替尼在大鼠体内药动学的影响。结果：兰索拉唑未显著降低卡博替尼的AUC_0-∞、C_max和t_max等药动学指标，且大鼠给药4 h后，在其血中浓度逐渐增加并慢慢接近峰值，在组织中分布顺序为肝 > 肺 > 肾；给药6 h后，在肝组织中浓度慢慢接近峰值，兰索拉唑对卡博替尼体内各组织分布情况并无明显影响。结论：兰索拉唑并未影响卡博替尼在大鼠体内的吸收及小鼠组织中的分布，对质子泵抑制剂（PPI）类药物会影响pH依赖性药物体内吸收的研究有一定的意义。

Effect of lansoprazole on the pharmacokinetics of cabozantinib in rats

OBJECTIVE To evaluate the effect of lansoprazole on the pharmacokinetics of cabozantinib in rats. METHODS Sixteen rats were divided into two groups:namely CBZ+0.9% saline solution, CBZ+lansoprazole (8 mg·kg^-1·d^-1). Plasma concentration and tissue distribution of CBZ were determined by HPLC-MS/MS. RESULTS The main pharmacokinetic parameters AUC_0-∞,C_max and t_max were not decreased significantly. Blood levels of CBZ at 4 h post-dosing gradually increased and approached peak levels. Tissue concentrations of CBZ were in the order of liver > lung > kidney, and concentration of CBZ in liver at 6 h post-dosing approached peak levels. Lansoprazole had little effects on the tissue distribution of CBZ. CONCLUSION The oral absorption and tissue distribution of CBZ are not inhibited obviously by lansoprazole, which has certain significance in the effect of oral absorption of pH-dependent drugs by PPIs.