缬沙坦对参麦注射液在大鼠体内药动学影响的研究

Impacts of Valsartan on In Vivo Pharmacokinetics in the Rats with Shenmai Injection

目的探讨缬沙坦对参麦注射液在大鼠体内药动学的影响。方法 12只Wistar大鼠随机分为单独给药组(参麦注射液9.00 ml/kg,静脉给药)和联合给药组(生脉注射液联用缬沙坦,15mg/kg)。在给药前和给药后0.083、0.25、0.5、0.75、1、1.5、2、3、6、12、24、48、96、144 h采集血液样品。采用HPLC方法研究缬沙坦对参麦注射液中人参皂苷Rg1、Re、Rb1三种指标成分在大鼠体内药动学的影响。应用药动学软件DAS 2.0求算药动学参数,采用统计学软件SPSS 18.0对各组数据进行统计学分析。结果同单独给药组比较,联合给药组大鼠体内人参皂苷Rg1的血药浓度显著降低(P<0.01),在大鼠体内的Ke明显增加(P<0.05),CL升高(P<0.01),MRT明显缩短(P<0.01),t1/2明显减小(P<0.05),导致AUC(0-144)显著降低(P<0.01);人参皂苷Re在大鼠体内的药动学参数没有显著性变化;人参皂苷Rb1的血药浓度明显升高,Ke明显降低(P<0.01),MRT延长(P<0.05),CL降低(P<0.05),t1/2延长(P<0.01),因此AUC(0-144)显著升高(P<0.01)。结论缬沙坦增加了人参皂苷Rb1的血药浓度,减慢了其在大鼠体内的清除过程,同时降低了人参皂苷Rg1在大鼠体内的血药浓度,加快其在体内的清除。联合用药并没有影响Re在大鼠体内的血药浓度。

Objective To explore the impacts of valsartan on in vivo pharmacokinetics in the rats with shenmai injection. Methods Twelve Wistar rats were randomized into a single medication group（shenmai injection 9. 00 ml/ kg,intravenous administration）and a combined medication group（shenmai injection com-bined with valsartan,15 mg/ kg,oral administration）. Blood samples were collected before medication and 0. 083 h,0. 25 h,0. 5 h,0. 75 h,1 h,1. 5 h,2 h,3 h,6 h,12 h,24 h,48 h,96 h and 144 h after medication. HPLC was adopted to study the impacts of valsartan on Rg1 ,Re and Rb1 in ginsenoside of shenmai injection in pharmacokinetics in vivo of the rats. DAS2. 0 was used to calculate pharmacokinetics parameters. SPSS 18. 0 was used for the statistical analysis of data in each group. Results Compared with the single medica-tion group,the blood concentration of in vivo ginsenoside Rg1 was reduced significantly in the combined med-ication group（P ﹤ 0. 01）,Ke was increased apparently（P ﹤ 0. 05）,CL was increased（P ﹤ 0. 01）,MRT was shortened apparently（P ﹤ 0. 01）,t1 / 2 was reduced apparently（P ﹤ 0. 05）,resulting in the significant decrease of AUC（0 - 144）. The in vivo pharmacokinetics parameters of ginsenoside Re did not change significantly. Blood concentration of ginsenoside Rb1 was increased apparently,Ke was reduced apparently（P ﹤ 0. 01）, MRT was prolonged（P ﹤ 0. 05）,CL was reduced（P ﹤ 0. 05）,t1 / 2 was prolonged（P ﹤ 0. 01）,resulting in the significant increase of AUC（0 - 144）. Conclusion Valsartan increases blood concentration of ginsenoside Rb1 and reduces its clearing;at same time,it decreases blood concentration of ginsenoside Rg1 and accelerates its clearing in the rats. The combined medication does not affect in vivo blood concentration of Re in the rats.