雷贝拉唑对大鼠体内稳态时氯吡格雷药动学的影响  

Effect of Rabeprazole on Steady-State Pharmacokinetics of Clopidogrel in Rats

作　　者：吴伟明[1] 黄成坷[1] 王军[1] 戴歌心[2] 王增寿[1] 

机构地区：[1]温州医学院附属第二医院药学部,浙江温州325027 [2]温州医学院附属第一医院药学部,浙江温州325000

出　　处：《中国药学杂志》2013年第4期289-292,共4页Chinese Pharmaceutical Journal

基　　金：温州市科技计划项目(Y20100262)

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。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 ） , rabeprazale （8 mg· kg - 1 . d - 1 ） ＋ clopidogrel （ 30 mg· kg - 1 . d - 1 ）, omeprazole （ 8 mg · kg - 1· d - 1 ） ＋ clopidogrel （ 30 mg·kg- l . d - l ） 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, tl/2z, CLz/F, pmaxand pmax（P 〉0. 05 ）, except that the tin, 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 elopidogrel to SR26334 , but there is no significant influence on the degree of metabolisrru

关 键 词：氯吡格雷 雷贝拉唑 奥美拉唑 SR26334 药动学 药物相互作用 

分 类 号：R969.1[医药卫生—药理学]