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 investigate the effects of intestinal flora on the pharmacokinetics of clopidogrel hydrogen sulfate and its active metabolites in rats. Methods: Twenty-four healthy rats were randomly divided into probiotics group, antibiotic group and control group, with 8 mice in each group. The mice were inoculated with viable Lactobacillus bifidobacterium (0.8 g · kg -1) Xilin and Clavulanate tablets (125 mg · kg -1) and an equal volume of purified water for 7 days. On the 8th day, the clopidogrel bisulfate tablets were given, and the blood was taken from the anticoagulant tubes containing the derivatizing agent before administration and at different time points after administration. The blood concentration was determined by LC-MS / MS, , Using the DAS 2.1.1 fitting pharmacokinetic parameters, SPSS 21.0 for statistical comparison. RESULTS: The main pharmacokinetic parameters AUC_ (0-t), AUC_ (0-∞), t_ (1/2), and the relative bioavailability of clopidogrel bisulfate and active metabolite derivatives (CAMD) ), T_ (max), CL, V, C_ (max) were not statistically different (P> 0.05). Conclusion: The change of intestinal flora has no effect on the pharmacokinetic parameters of clopidogrel hydrogen sulfate and its active metabolites.