奥美拉唑对氯吡格雷在大鼠体内药动学特征的影响  

Effects of omeprazole on pharmacokinetics of clopidogrel in rats

作　　者：付翠香[1] 王军[1] 吴伟明[1] 王增寿[1] 

机构地区：[1]温州医学院附属第二医院药学部,温州325027

出　　处：《中国临床药学杂志》2013年第3期143-146,共4页Chinese Journal of Clinical Pharmacy

摘　　要：目的研究奥美拉唑对大鼠体内氯吡格雷药动学特征的影响。方法将16只SD大鼠随机分成2组,单用组(氯吡格雷溶液30 mg·kg^(-1)·d^(-1),ig×7 d)和联用组(氯吡格雷溶液30 mg·kg^(-1)·d^(-1)+奥美拉唑溶液8 mg·kg^(-1)·d^(-1),ig×7 d)。于给药后不同时间点采集血样,用HPLC-DAD法测定血浆中氯吡格雷代谢产物SR26334的浓度;用DAS药动学软件对SR26334血药浓度-时间数据采用非房室模型分析,求得氯吡格雷在大鼠体内主要的药动学参数,并对其进行统计分析。结果联用组大鼠药动学参数AUC_(0→48h)、AUC_(0→∞)、MRT_(0→48h)和CLz/F等与单用组比较差异均有统计学意义,其中AUC_(0→48h)和AUC_(0→∞)增加了约20%(P<0.05),SR26334在体内的滞留时间MRT(0→48h)显著延长(P<0.01),CLz/F下降了20%。结论奥美拉唑不仅显著增加了CL在大鼠体内代谢为SR26334速度,而且对于其代谢程度也有显著性影响。AIM To study the effect of omeprazole on pharmacokinetics of clopidogrel in rats. METHODS A to tal of 16 rats were divided into 2 groups： single drug group（ clopidogrel solution 30 rag. kg- 1. d- 1, ig x 7 d） and combined omprazole group（ clopidogrel solution 30 mg. kg- 1. d- 1 ＋ omeprazole solution 8 mg.kg- 1. d- 1, ig x 7 d）. Concentrations of clopidogrel metabolite SR26334 in plasma were determined by I-IPLC-DAD. The plasma concentration-time data of SR26334 were analyzed by DAS program according to no-compartment model. The main phannacokinetic parameters of SR26334 were obtained and compared with SPSS software between 2 groups. RESULTS There was significant difference between the single drug group and the combined omeprazole group in the main pharmacokinetic parameters of SR26334, the AUC0→48h and AUCo→∞ of combined omeprazole group increased about 20 % （ P 〈 0.05 ）, MRT0∞48h significantly prolonged （P 〈 0.01） and CLz/F decreased about 20% （P 〈 0.05）. CONCLUSION There is a significant effect of omeprazole on pharmacokinetics of clopidogrel in rats. Omeprazole can accelerate clopidogrel metabolism for SR26334 in vivo, and has a significant influence on its degree of metabolism.

关 键 词：氯吡格雷 奥美拉唑 SR26334 药动学 

分 类 号：R96[医药卫生—药理学]