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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 pharmacokinetics of clopidogrel in rats at home. Methods Twenty-eight healthy SD rats were randomly divided into 3 groups: clopidogrel (ig, 30 mg · kg -1 · d -1), rabeprazole (ig, 8 mg · kg -1 · d -1) + Clopidogrel (ig, 30 mg · kg -1 · d -1), omeprazole (ig, 8 mg · kg -1 · d -1) + clopidogrel (ig, 30 mg · kg -1 · D-1) for 7 days. Blood samples were collected at different time points after administration. The concentration of clopidogrel carboxylic acid metabolite SR26334 in plasma was determined by HPLC-DAD. The data of the plasma concentration of D-galactose were measured by DAS3.0. The main pharmacokinetic parameters were calculated and compared. Results There were no significant differences in the main pharmacokinetic parameters AUC0-t, AUC0-∞, MRT0-t, t1 / 2z, CLz / F, ρmax and ρss in rabeprazole group (P <0.05). The tmax decreased from (1.17 ± 0.41) h to (0.58 ± 0.20) h (P <0.01), and the AUC0-t and AUC0-∞ increased by about 20% -t significantly prolonged (P <0.01), CLz / F decreased by 20% (P <0.05). Conclusion Long-term co-administration of rabeprazole accelerates the in vivo metabolism of clopidogrel to SR26334, but has no significant effect on its metabolism.