酒石酸美托洛尔连续给药大鼠体内药动学研究  

Effects of continuously taking metoprolol tartrate on the pharmacokinetics in rats

作　　者：张亚坤[1] 王伟美 贡莹[1] 张欢[1] 张志清[1] 

机构地区：[1]河北医科大学第二医院药学部,河北石家庄050000

出　　处：《河北医科大学学报》2016年第3期309-312,共4页Journal of Hebei Medical University

摘　　要：目的观察连续服用酒石酸美托洛尔(metoprolol tartrate,MT)片6d后大鼠体内药动学变化。方法将40只大鼠随机分为2组各20只。实验组灌胃酒石酸MT 27mg/kg每天1次,连续6d;对照组灌胃等量蒸馏水每天1次,连续6d。2组于第7天同时灌胃酒石酸MT(27mg/kg)后5h内眼内眦取血,血浆样品处理后用超高效液相色谱法(ultra performance liquid chromatography,UPLC)测定并绘制药时曲线,并用DAS 2.1.1软件拟合药动学参数,采用SPSS 13.1软件对2组药动学参数进行统计学分析。结果实验组与对照组主要药动学参数:血药浓度时间曲线下面积(area under curve,AUC)0~5h分别为(0.84±0.40)mg·h^(-1)·L^(-1)和(0.96±0.46)mg·h^(-1)·L^(-1);AUC0~∞分别为(0.91±0.41)mg·h^(-1)·L^(-1)和(1.05±0.50)mg·h^(-1)·L^(-1);药物消除半衰期(half life,t1/2)分别为(1.23±0.36)h和(1.42±0.41)h;达峰时间(Tmax)分别为(0.51±0.10)h和(0.85±0.28)h;表观分布容积(V)分别为(58.19±22.61)L/kg和(61.54±30.55)L/kg;血浆清除率(plasma clearance,CL)分别为(33.94±13.59)L·h^(-1)·kg^(-1)和(30.07±11.20)L·h^(-1)·kg^(-1);血药峰浓度(peak concentration,Cmax)分别为(0.71±0.40)mg/L和(0.64±0.35)mg/L。2组间Tmax和Cmax差异有统计学意义,其他药动学参数AUC0~5h、AUC0~∞、t1/2、CL、V差异无统计学意义(P>0.05)。结论连续灌胃酒石酸MT片6d后,其在大鼠体内未见蓄积且达峰时间缩短。Objective To investigate the changes of continuous administration of metoprolol tartrate tablets in six days on the pharmacokinetic of in rats.Methods Forty rats were randomly divided into two groups with 20 rats in each group.Each rat in the test group was given metoprolol tartrate（27 mg/kg）,and each rat in the control group was given equal volume of distilled water orally,twice daily for 6days.On day 7,each rat in two groups recieved a single dose of metoprolol tartrate（27 mg/kg）.Blood samples were taken at different times after administration from the inner canthus.The concentrations of metoprolol tartrate were determined by ultra performance liquid chromatography（UPLC）.The pharmacokinetic parameters of the two groups were calculated with DAS 2.1.1pharmacokinetic software and were compared with SPSS13.1software.Results The main pharmacokinetic parameters in the test group and control group：area under curve（AUC）0-5hwere（0.84±0.40）mg·h^-1·L^-1 and（0.96±0.46）mg·h^-1·L^-1,respectively;AUC0-∞were（0.91±0.41）mg·h^-1·L^-1 and（1.05±0.50）mg·h^-1·L^-1,respectively;half life（t1/2）were（1.23±0.36）h and（1.42±0.41）h,respectively;Tmax were（0.51±0.10）h and（0.85±0.28）h,respectively;V were（58.19±22.61）L/kg and（61.54±30.55）L/kg,respectively;plasma clearance（CL）were（33.94±13.59）L·h^-1·kg^-1and（30.07±11.20）L·h^-1·kg^-1,respectively;peak concentration（Cmax）were（0.71±0.40）mg/L and（0.64±0.35）mg/L,respectively.There were no significant differences in parameters of AUC0-5h,AUC0-∞,t1/2,CL,V between control group and test group（P0.05）.There were significant difference in Tmaxand Cmaxbetween two groups.Conclusion There has no accumulation and Tmax was shortened in rats given metoprolol tartrate for six days.

关 键 词：美托洛尔 药代动力学 超高效液相色谱法 大鼠 

分 类 号：R971.94[医药卫生—药品]