Evaluation of the Effects of Apatinib on the Pharmacokinetics of Venlafaxine and O-desmethylvenlafaxine in SD Male Rats by UPLC-MS/MS
Evaluation of the Effects of Apatinib on the Pharmacokinetics of Venlafaxine and O-desmethylvenlafaxine in SD Male Rats by UPLC-MS/MS
复制标题
DOI：
10.1111/bcpt.13081
复制
发表时间：
2018-12-01
影响因子：
3.1
通讯作者：
Hu, Guo-xin
中科院分区：
文献类型：
--
作者：
Bao, Su-su;Wen, Jian;Hu, Guo-xin
本研究的目的是评价阿帕替尼对SD大鼠中文拉法辛和O-去甲基文拉法辛药代动力学的影响，以及阿帕替尼对大鼠和人肝微粒体中文拉法辛的抑制作用。将21只SD雄性大鼠随机分为3组（n = 7）：A组（40 mg/kg阿帕替尼多次给药7天）、B组（40 mg/kg阿帕替尼单次给药）和C组（对照组）。结果表明，阿帕替尼单次给药后，文拉法辛和O-去甲基文拉法辛的AUC（0-t）、AUC（0-infinity）和C-max均显著增加，而Vz/F和CLz/F降低。A组仅文拉法辛的AUC（0-t）和CLz/F发生变化，而O-去甲基文拉法辛的参数无变化。此外，阿帕替尼被确定为文拉法辛的混合抑制剂。
The objective of this study was to evaluate the effect of apatinib on the pharmacokinetics of venlafaxine and O-desmethylvenlafaxine in SD rats and the inhibitory effects of apatinib on venlafaxine in rat and human liver microsomes. Twenty-one SD male rats were randomly divided into three groups (n = 7): group A (multiple dose of 40 mg/kg apatinib for 7 days), group B (single dose of 40 mg/kg apatinib) and group C (the control group). All samples were measured by UPLC-MS/MS. The results indicated that a single dose of apatinib increased the AUC((0-t)), AUC((0-infinity)) and C-max of both venlafaxine and O-desmethylvenlafaxine significantly, while Vz/F and CLz/F were decreased. As for group A, only AUC((0-t)) and CLz/F of venlafaxine were changed, while no parameters of O-desmethylvenlafaxine were altered. In addition, apatinib was determined to be a mixed inhibitor of venlafaxine.