氨氯地平对替格瑞洛在大鼠体内药动学的影响研究

Effect of Amlodipine on the Pharmacokinetics of Ticagrelor in Rats

目的探索氨氯地平对替格瑞洛在大鼠体内药动学的影响。方法随机将大鼠分为两组,分别给予替格瑞洛单药灌胃及替格瑞洛与氨氯地平灌胃,采用LC-MS/MS法对两组血浆样品中替格瑞洛的药物浓度进行测定。以PK Solver 2.0程序软件拟合药动学参数并进行比较。结果大鼠服药后2 h替格瑞洛血药浓度达到峰值,同时给药氨氯地平后,其血药浓度增加,C_(max)、AUC显著增大,CL显著降低(P<0.05)。结论所建立的LC-MS/MS法具有专属性良好、准确性和灵敏性高的特点。联用氨氯地平对替格瑞洛的体内药动学特性有显著影响。

Objective To study the effect of amlodipine on the pharmacokinetics of ticagrelor in rats. Methods Rats were randomly divided into two equal groups, one group was given ticagrelor, and the other was given ticagrelor and amlodipine. Blood samples were taken from the animals for the determination of the plasma concentration of ticagrelor by LC-MS/MS. The pharmacokinetics parameters were calculated using PK Solver 2.0 program to evaluate each of the two preparations and statistically compared. Results The plasma concentration-time course showed an increased dose of ticagrelor in rats after 2 h, Cmax and AUC has a significant increase, while CL has a significant decrease(P<0.05). Conclusion The LC-MS/MS method we established has high specificity, accuracy and sensitivity. The combination of ticagrelor and amlodipine has significant effect on the pharmacokinetics of ticagrelor.