【摘要】 目的研究雷贝拉唑对氯吡格雷在大鼠体内稳态时药动学的影响。方法 18只健康SD大鼠随机分成3组,分别给予氯吡格雷(ig,30 mg·kg-1·d-1)、雷贝拉唑(ig,8 mg·kg-1·d-1)+氯吡格雷(ig,30 mg·kg-1·d-1)、奥美拉唑(ig,8 mg·kg-1·d-1)+氯吡格雷(ig,30 mg·kg-1·d-1),连续7 d。于给药后不同时间点采集血样,用HPLC-DAD测定血浆中氯吡格雷羧酸代谢物SR26334的浓度,用DAS3.0处理经时血药浓度数据,计算主要药动学参数并进行比较。结果与单用组比较,雷贝拉唑组的主要药动学参数AUC0-t,AUC0-∞,MRT0-t,t1/2z,CLz/F,ρmax和ρss差异均无统计学意义(P>0.05),tmax由(1.17±0.41)h减少为(0.58±0.20)h(P<0.01);奥美拉唑组的AUC0-t和AUC0-∞增加了约20%(P<0.05),MRT0-t显著延长(P<0.01),CLz/F下降了20%(P<0.05)。结论长期合用雷贝拉唑后可以加快氯吡格雷体内代谢为SR26334的速度,但对于其代谢程度没有显著性影响。更多还原

【Abstract】 OBJECTIVE To study the effect of rabeprazole on the steady-state pharmacokinetics of clopidogrel in rats.METHODS Eighteen healthy SD rats were divided into three groups,which were intragastricly administered clopidogrel(30 mg·kg-1·d-1),rabeprazole(8 mg·kg-1·d-1) + clopidogrel(30 mg·kg-1·d-1),omeprazole(8 mg·kg-1·d-1) + clopidogrel(30 mg·kg-1·d-1) respectively for 7 d.The plasma concentrations of the metabolite of clopidogrel,SR26334,were determined by HPLC-DAD.The pharmacokinetic parameters of SR26334 were obtained with statistical analysis by DAS 3.0.RESULTS There was no significant difference between the single-drug group and the rabeprazole combination group in the main pharmacokinetic parameters of SR26334,such as AUC0-t,AUC0-∞,MRT0-t,t1/2z,CLz/F,ρmax and ρss(P>0.05),except that the tmax significantly decreased from(1.17±0.41) h in the single-drug group to(0.58±0.20) h in the combination group(P<0.01).Compared with single-drug group,the AUC0-t and AUC0-∞of the omeprazole combination group increased for about 20%(P<0.05),MRT0-t significantly prolonged(P<0.01),and CLz/F decreased for about 20%(P<0.05).CONCLUSION Long-term combinaton treatment with rabeprazole can accelerate the in vivo metabolism of clopidogrel to SR26334,but there is no significant influence on the degree of metabolism.更多还原