The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
Wenzhou Medical University, Wenzhou 325035, China.
Biomed Res Int. 2017;2017:3619723. doi: 10.1155/2017/3619723. Epub 2017 Dec 26.
The present study aimed to investigate the effect of anlotinib (AL3818) on pharmacokinetics of cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C6, CYP2D1, CYP2D2, and CYP3A1/2) by using five cocktail probe drugs in vivo. After pretreatment for 7 days with anlotinib (treatment group) or saline (control group) by oral administration, probe drugs phenacetin, tolbutamide, omeprazole, metoprolol, and midazolam were administered to rats by oral administration. Blood samples were obtained at a series of time-points and the concentrations of five probe drugs in plasma were determined by a UHPLC-MS/MS method. The results showed that treatment with anlotinib had no significant effect on rat CYP1A2, CYP2D2, and CYP2C6. However, anlotinib had a significant inductive effect on CYP2D1 and CYP3A1/2. Therefore, caution is needed during the concomitant use of anlotinib with other drugs metabolized by CYP2D1 and CYP3A1/2 because of potential drug-anlotinib interactions.
本研究旨在通过体内五种鸡尾酒探针药物来研究安罗替尼（AL3818）对细胞色素 P450（CYP）酶（CYP1A2、CYP2C6、CYP2D1、CYP2D2 和 CYP3A1/2）的药代动力学的影响。通过口服给予安罗替尼（治疗组）或生理盐水（对照组）预处理 7 天后，通过口服给予探针药物非那西丁、甲苯磺丁脲、奥美拉唑、美托洛尔和咪达唑仑。在一系列时间点采集血样，并通过 UHPLC-MS/MS 方法测定血浆中五种探针药物的浓度。结果表明，安罗替尼治疗对大鼠 CYP1A2、CYP2D2 和 CYP2C6 没有显著影响。然而，安罗替尼对 CYP2D1 和 CYP3A1/2 有显著的诱导作用。因此，由于潜在的药物-安罗替尼相互作用，在与其他经 CYP2D1 和 CYP3A1/2 代谢的药物同时使用时需要谨慎。
