肠道菌群对硫酸氢氯吡格雷及其活性代谢产物在大鼠体内药动学的影响

Effect of the intestinal flora on the pharmacokinetics of clopidogrel bisulfate and its active metabolite in rats

目的:探究肠道菌群变化对硫酸氢氯吡格雷及其活性代谢产物在大鼠体内药动学的影响。方法:24只健康大鼠随机分为益生菌组、抗生素组和对照组,每组8只,分别灌胃双歧杆菌乳杆菌三联活菌(0.8 g·kg^(-1))、阿莫西林克拉维酸钾片(125mg·kg^(-1))和等体积的纯化水,连续7 d。第8天给予硫酸氢氯吡格雷片,并于给药前和给药后不同时间点取血于含有衍生试剂的抗凝管中,LC-MS/MS法测定血药浓度,绘制药时曲线,使用DAS 2.1.1拟合药动学参数,SPSS 21.0进行统计学比较。结果:益生菌组、抗生素组和对照组硫酸氢氯吡格雷和活性代谢产物衍生物(CAMD)的主要药动学参数AUC_(0-t)、AUC_(0-∞)、t_(1/2)、t_(max)、CL、V、C_(max)均没有统计学差异(P>0.05)。结论:肠道菌群变化对硫酸氢氯吡格雷及其活性代谢产物的药动学参数没有影响。

OBJECTIVE To study the effect of intestinal flora on the pharmacokinetics of clopidogrel bisulfate and its active metabolite in rats.METHODS Twenty four SD rats were randomly divided into probiotic group,antibiotics group and control group.Eight rats in each group which orally given live combined Bifidobacterium and Lactobacillus tablets （0.8 g·kg^-1）,amoxicillin and clavulanate potassium tablets （125 mg·kg^-1） and the same volume of distilled water for 7 days,respectively.On day 8,clopidogrel bisulfate was administered orally to all rats.Blood samples were collected for pharmacokinetic study at different time points after clopidogrel bisulfate administration.The plasma concentrations of clopidogrel bisulfate and its metabolite （CAMD） were determined by LC-MS/MS.The pharmacokinetic parameters were determined by DAS 2.1.1 software and the statistical analysis was processed with SPSS 21.0 software.RESULTS The main pharmacokinetic parameters such as AUC0-t,AUC0-∞,t1/2,tmax,CL,V,Cmax of clopidogrel bisulfate and CAMD in the probiotic group,antibiotics group and control group had no significant difference （P〉0.05）.CONCLUSION Intestinal flora has no significant influence on the pharmacokinetics of clopidogrel bisulfate and its active metabolite.