盐酸沙格雷酯对酒石酸美托洛尔大鼠体内药动学的影响

目的:考察盐酸沙格雷酯与酒石酸美托洛尔合用6 d后,酒石酸美托洛尔在大鼠体内药动学变化。方法:将40只大鼠随机分为实验组和对照组,每组20只,实验组灌胃盐酸沙格雷酯(10 mg·kg)每天3次和酒石酸美托洛尔(27 mg·kg^-1)每天一次,连续6 d;对照组灌胃酒石酸美托洛尔(27 mg·kg^-1)每天一次,连续6 d。2组于第7天灌胃给药后5 h内眼内眦取血,血浆样品处理后用UPLC-UV测定并绘制相应的药时曲线,DAS 2.1.1软件拟合药动学参数后,用SPSS 13.1软件对2组药动学参数做统计学分析。结果:实验组和对照组主要药动学参数如下:AUC_0-5h分别为(0.98±0.41) mg·h·L^-1和(0.84±0.40) mg·h·L^-1;AUC_0-∞分别为(1.08±0.42) mg·h·L^-1和(0.91±0.41) mg·h·L^-1;t_1/2分别为(1.40±0.36) h和(1.23±0.36)h;t_max分别为(0.66±0.31)h和(0.51±0.10)h;V分别为(57.02±23.46)L·kg^-1和(58.19±22.61)L·kg^-1 ;CL分别为(28.60±10.89)L·h^-1·kg^-1和(33.94±13.59)L·h^-1·kg^-1;C_max分别为(0.62±0.39)mg·L^-1和(0.71±0.40)mg·L^-1。数据显示2组间无显著性差异(P>0.05)。结论:盐酸沙格雷酯与酒石酸美托洛尔合用6 d前后,酒石酸美托洛尔在大鼠体内的药动学参数无显著性变化。

Effects of sarpogrelate hydrochloride on the pharmacokinetics of metoprolol tartrate in rats

OBJECTIVE To investigate the influence of sarpogrelate hydrochloride on the pharmacokinetic of metoprolol tartrate in rats.METHODS All rats were randomly divided into control group and test group with 20 rats in each group.The experimental group was intragastric administration with metoprolol tartrate(27 mg·kg^-1) once a day and sarpogrelate hydrochloride (10 mg·kg^-1) three time a day; the control group was intragastric administration with metoprolol tartrate(27 mg·kg^-1) once a day,continue to lavage in six days.Immediately take blood from the inner canthus in five hours.The plasma concentrations of metoprolol tartrate were measured by UPLC-UV.The pharmacokinetic parameters of the two groups were computed and compared.RESULTS Experimental group and control group the main pharmacokinetic parameter:AUC_0-5h were (0.98±0.41) mg·h·L^-1 and (0.84±0.40) mg·h·L^-1; AUC_0-∞were (1.08±0.42) mg·h·L^-1and (0.91±0.41) mg·h·L^-1 ; t_1/2were (1.40±0.36) h and (1.23±0.36) h; t_max were (0.66±0.31) h and (0.51±0.10) h; V were (57.02±23.46)L·kg^-1 and (58.19±22.61) L·kg^-1 ;CL were (28.60±10.89) L·h^-1·kg^-1 and (33.94±13.59) L·h^-1·kg^-1;C_max were (0.62±0.39) mg·L^-1 and (0.71±0.40) mg·L^-1.There was no significant difference between the control group and test group (P>0.05).CONCLUSION The pharmacokinetics of metoprolol tartrate in rats has no significant change before and after combining sarpogrelate hydrochloride.