School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
Basic Clin Pharmacol Toxicol. 2018 Dec;123(6):721-726. doi: 10.1111/bcpt.13081. Epub 2018 Aug 2.
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 , AUC and C of both venlafaxine and O-desmethylvenlafaxine significantly, while Vz/F and CLz/F were decreased. As for group A, only AUC 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.
本研究旨在评估阿帕替尼对 SD 大鼠文拉法辛及其 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。21 只雄性 SD 大鼠随机分为三组（n = 7）：A 组（连续 7 天给予 40mg/kg 阿帕替尼的多剂量组）、B 组（单次给予 40mg/kg 阿帕替尼的单剂量组）和 C 组（对照组）。所有样本均采用 UPLC-MS/MS 进行测量。结果表明，单次给予阿帕替尼可显著增加文拉法辛及其 O-去甲基文拉法辛的 AUC 、 AUC 和 C ，同时降低 Vz/F 和 CLz/F。对于 A 组，只有文拉法辛的 AUC 和 CLz/F 发生改变，而 O-去甲基文拉法辛的任何参数均未改变。此外，阿帕替尼被确定为文拉法辛的混合抑制剂。
