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  

Pharmacokinetic interaction study between sorafenib and dapagliflozin in rats

作　　者：何雪茹 李颖[2] 马银玲[2] 付裕豪 荀雪姣 董占军[2] HE Xueru;LI Ying;MA Yinling;FU Yuhao;XUN Xuejiao;DONG Zhanjun(Graduate School of Hebei Medical University,Shijiazhuang 050011,Hebei,China;Department of Pharmacy,Hebei Provincial People's Hospital,Shijiazhuang 050057,Hebei,China)

机构地区：[1]河北医科大学研究生院,河北石家庄050011 [2]河北省人民医院药学部,河北石家庄050057

出　　处：《中国临床药理学与治疗学》2023年第5期498-507,共10页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：河北省医学科学研究课题(20210037)。

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C_(max)、AUC_(0-t)和AUC_(0-∞)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。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-tan-dem 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 pa-rameters were calculated by compartment model.RESULTS:1 mg/kg dapagliflozin increased the C_(max),AUC_(0-t) and AUC_(0-∞) of sorafenib by 52.5%,38.1%and 37.7%,respectively,and 0.5 mg/kg dapagliflozin in-creased the AUC0-t and AUC_(0-∞) of sorafenib by 36.3%and 36.3%.CONCLUSION:Pharmacokinetic interac-tions may exist between sorafenib and dapa-gliflozin,active surveillance for treatment and toxic-ity should be required when the two drugs com-bined together in clinical practice.

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 

分 类 号：R965.2[医药卫生—药理学]