谷红注射液主要有效成分在脑缺血模型大鼠体内的药动学研究

Pharmacokinetics of main activ ingredients of Guhong injection in cerebral ischemia rats

为研究谷红注射液有效成分在脑缺血再灌注损伤大鼠体内的药动学特征,该实验以大鼠大脑中动脉局灶性栓塞（MCAO）模型,尾静脉给予谷红注射液（2.1 m L·kg-1）后,采用高效液相色谱法（HPLC）测定不同时间点乙酰谷酰胺和羟基红花黄色素A（HSYA）的血药浓度,绘制药时曲线并采用药动学软件DAS 3.2.6得到药动学参数。结果发现,乙酰谷酰胺和HSYA分别在1.5500 mg·L-1（R2=0.997 5）和0.3340 mg·L-1（R2=0.998 9）的质量浓度内呈良好线性关系,该方法的回收率高,精密度、稳定性良好;两者的主要药动学参数t1/2α,t1/2β,CL1,CL2,AUC0-t,AUC0-∞,Vd1,Vd2分别为（0.139±0.007）和（0.155±0.017）h,（0.803±0.046）和（2.233±0.410）h,（0.016±0）和（0.149±0.018）L·h-1·kg-1,（0.015±0.001）和（0.446±0.016）L·h-1·kg-1,（133.335±3.844）和（9.298±0.179）mg·h·L-1,（143.851±3.595）和（14.464±1.451）mg·h·L-1,（0.009±0.001）和（0.223±0.007）L·kg-1,（0.006±0.001）和（0.212±0.032）L·kg-1。表明所建立的HPLC专属性强,可用于谷红注射液中乙酰谷酰胺和HSYA在MCAO大鼠体内的同时检测和药动学研究;药动学参数可以为连续给药、间隔给药提供参考依据。

To investigate the pharmacokinetic characteristics of active constituents of Guhong injection in rats with cerebral ischemia reperfusion injury. The middle cerebral artery occlusion（ MCAO） model was established in our studies,and then all the rats received iv administration of Guhong injection（ 2. 1 m L·kg-1）. The blood concentrations of aceglutamide and hydroxysafflor yellow A（ HSYA）were determined by high performance liquid chromatography（ HPLC） method at different time points. The concentration-time curves were drawn and pharmacokinetic data were obtained by DAS 3. 2. 6 software. The results showed that aceglutamide and HSYA showed good linear relationship within the ranges of 1. 5-500 mg·L-1（ R2= 0. 997 5） and 0. 33-40 mg·L-1（ R2= 0. 998 9） respectively. This quantitative method showed a high recovery rate,good precision and stability. The main pharmacokinetics parameters of t1/2α,t1/2β,CL1,CL2,AUC0-t,AUC0-∞,Vd1,and Vd2 were（ 0. 139 ± 0. 007） and（ 0. 155 ± 0. 017） h,（ 0. 803 ± 0. 046） and（ 2. 233 ± 0. 410）h,（ 0. 016 ± 0） and（ 0. 149 ± 0. 018） L·h-1·kg-1,（ 0. 015 ± 0. 001） and（ 0. 446 ± 0. 016） L·h-1·kg-1,（ 133. 335 ± 3. 844） and（ 9. 298 ± 0. 179） mg·h·L-1,（ 143. 851 ± 3. 595） and（ 14. 464 ± 1. 451） mg·h·L-1,（ 0. 009 ± 0. 001） and（ 0. 223 ± 0. 007） L·kg-1,（ 0. 006 ± 0. 001） and（ 0. 212 ± 0. 032） L·kg-1,respectively. The results showed that the established HPLC method was highly specific,and could be used for the simultaneous detection of aceglutamide and HSYA of Guhong injection in MCAO rats,which was conducive to pharmacokinetic studies. Pharmacokinetic data and parameters could provide reference for continuous administration and interval administration of the drug.