瑞舒伐他汀和替格瑞洛在大鼠体内的药动学相互作用  

Pharmacokinetic Interactions Between Rosuvastatin and Ticagrelor in Rats

作　　者：田雨 Tian Yu(The Third Affiliated Hospital of Jinzhou Medical University,Jinzhou 121000 China)

机构地区：[1]锦州医科大学附属第三医院,辽宁锦州121000

出　　处：《锦州医科大学学报》2022年第5期23-28,共6页Journal of Jinzhou Medical University

摘　　要：目的建立LC-MS/MS法同时测定大鼠血浆中瑞舒伐他汀和替格瑞洛的浓度,考察二者的药动学相互作用。方法将大鼠随机分为单用瑞舒伐他汀组、单用替格瑞洛组及联合用药组,通过LC-MS/MS法测定给药后多个时间点的血药浓度,采用WinNonlin 8.1软件计算药动学参数,SPSS 24.0软件进行统计分析。结果同单独用药组相比,联合用药后瑞舒伐他汀的C_(max)、AUC_(0-t)、AUC_(0-∞)、MRT_(0-t)和MRT_(0-∞)显著升高,而Cl显著降低;替格瑞洛的T_(max)和MRT_(0-t)显著缩短。结论两药联用后药动学特征出现明显变化,替格瑞洛可导致瑞舒伐他汀在大鼠体内的暴露量增加,提示临床在联合用药时应密切关注不良反应的发生情况,必要时可调整给药剂量和间隔。Objective To determine the concentration of ticagrelor and rosuvastatin in rat plasma by establishing LC-MS/MS method and study the pharmacokinetic interactions between them.Methods Rats were randomly divided into the single ticagrelor group,the single rosuvastatin group and the combination group.The blood concentrations were measured by LC-MS/MS method at multiple time points after administration.The pharmacokinetic parameters were calculated with WinNonlin 8.1 software and statistically analyzed with SPSS 24.0.Results Compared with the single drug group,the C_(max),AUC_(0-t),AUC_(0-∞),MRT_(0-t)and MRT_(0-∞)of rosuvastatin were significantly higher after combined treatment,while CL was significantly lower,and the T_(max)and MRT_(0-t)of ticagrelor were significantly shorter.Conclusion The pharmacokinetic characteristics have changed significantly after combined treatment.Ticagrelor can lead to the increase of rosuvastatin exposure in rats,suggesting that the occurrence of adverse reactions should be closely paid attention to in clinical combination,and the dosage and interval of administration can be adjusted when necessary.

关 键 词：瑞舒伐他汀 替格瑞洛 LC-MS/MS 药动学相互作用 

分 类 号：R965[医药卫生—药理学]