欢迎访问《中国临床药理学与治疗学》杂志官方网站，今天是 分享到：

中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (5): 498-507.doi: 10.12092/j.issn.1009-2501.2023.05.003

• 基础研究 • 上一篇    下一篇

索拉非尼和达格列净在大鼠体中药代动力学相互作用研究

何雪茹1,2，李  颖2，马银玲2，付裕豪1,2，荀雪姣1,2，董占军2   

  1. 1河北医科大学研究生院，石家庄  050011，河北；2河北省人民医院药学部，石家庄  050057，河北
  • 收稿日期:2023-02-24 修回日期:2023-04-03 出版日期:2023-05-26 发布日期:2023-06-08
  • 通讯作者: 董占军，男，主任药师，硕士生导师，研究方向：临床药学。 E-mail: 13313213656@126.com
  • 作者简介:何雪茹，女，硕士，研究方向：临床药学。 E-mail: hxr9115@163.com
  • 基金资助:
    河北省医学科学研究课题（20210037）

Pharmacokinetic interaction study between sorafenib and dapagliflozin in rats

HE Xueru 1,2, LI Ying 2, MA Yinling 2, FU Yuhao 1,2, XUN Xuejiao 1,2, DONG Zhanjun 2   

  1. 1 Graduate School of Hebei Medical University, Shijiazhuang 050011, Hebei, China; 2 Department of Pharmacy, Hebei Provincial People's Hospital, Shijiazhuang 050057, Hebei, China
  • Received:2023-02-24 Revised:2023-04-03 Online:2023-05-26 Published:2023-06-08

PDF (PC)

135

摘要： 目的：探究索拉非尼与达格列净在大鼠体内的药代动力学相互作用，为临床合理使用两药提供参考。方法：建立同时测定大鼠血浆中索拉非尼和达格列净血药浓度的超高效液相色谱-串联质谱（UPLC/MS/MS）方法。雄性SD大鼠随机分为5组（每组6只），包括100 mg/kg索拉非尼组、0.5 mg/kg达格列净组、1 mg/kg达格列净组、100 mg/kg索拉非尼联合0.5 mg/kg达格列净组、100 mg/kg索拉非尼联合1 mg/kg达格列净组，用于索拉非尼和达格列净药物相互作用研究。所有的样品使用验证的UPLC/MS/MS方法进行分析，主要的药动学参数通过房室式模型计算。结果：1 mg/kg达格列净使索拉非尼的Cmax、AUC0-t和AUC0-∞分别增加了52.5%、38.1%和37.7%，0.5 mg/kg达格列净使索拉非尼的AUC0-t和AUC0-∞分别增加了36.3%和36.3%。结论：索拉非尼和达格列净联用时可能存在药代动力学相互作用，临床联合使用两药时应加强疗效和不良反应的监测。

关键词: 索拉非尼, 达格列净, 药物相互作用, 药代动力学, UPLC/MS/MS

Abstract:

AIM: To explore the pharmacokinetic interactions between sorafenib and dapagliflozin in rats and to provide some theoretical basis for the rational clinical use of the two drugs. METHODS: An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method was developed for the simultaneous determination of sorafenib and dapagliflozin. Male SD rats were randomly divided into 5 groups (6 rats in each group), including 100 mg/kg sorafenib group, 0.5 mg/kg dapagliflozin group, 1 mg/kg dapagliflozin group, and 100 mg/kg sorafenib combined with 0.5 mg/kg dapagliflozin group and 100 mg/kg sorafenib combined with 1 mg/kg dapagliflozin group, for sorafenib and dapagliflozin drug interaction study. All samples were analyzed using a validated UPLC/MS/MS method, and the main pharmacokinetic parameters were calculated by compartment model. RESULTS: 1 mg/kg dapagliflozin increased the Cmax, AUC0-t and AUC0-∞ of sorafenib by 52.5%, 38.1% and 37.7%, respectively, and 0.5 mg/kg dapagliflozin increased the AUC0-t and AUC0-∞ of sorafenib by 36.3% and 36.3%. CONCLUSION: Pharmacokinetic interactions may exist between sorafenib and dapagliflozin, active surveillance for treatment and toxicity should be required when the two drugs combined together in clinical practice.

Key words: sorafenib, dapagliflozin, drug interactions, pharmacokinetics, UPLC/MS/MS

中图分类号: 

版权所有 © 《中国临床药理学与治疗学》编辑部
地址：安徽省芜湖市皖南医学院弋矶山医院内　邮编：241001
电话：0553-5738350　 传真：0553- 5738350　 Email：cjcpt96@163.com
本系统由北京玛格泰克科技发展有限公司设计开发