雷贝拉唑对大鼠体内稳态时氯吡格雷药动学的影响

吴伟明, 黄成坷, 王军, 戴歌心, 王增寿*

中国药学杂志 ›› 2013, Vol. 48 ›› Issue (4) : 289-292.

中国药学杂志 ›› 2013, Vol. 48 ›› Issue (4) : 289-292. DOI: 10.11669/cpj.2013.04.011
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雷贝拉唑对大鼠体内稳态时氯吡格雷药动学的影响

  • 吴伟明1, 黄成坷1, 王军1, 戴歌心2, 王增寿1*
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Effect of Rabeprazole on Steady-State Pharmacokinetics of Clopidogrel in Rats

  • WU Wei-ming1 , HUANG Cheng-ke1, WANG Jun1, DAI Ge-xin2, WANG Zeng-shou1*
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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-tt1/2zCLz/Fρmax 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。

Abstract

1.Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, China;2.Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, Chin

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

Key words

?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.

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吴伟明, 黄成坷, 王军, 戴歌心, 王增寿*. 雷贝拉唑对大鼠体内稳态时氯吡格雷药动学的影响[J]. 中国药学杂志, 2013, 48(4): 289-292 https://doi.org/10.11669/cpj.2013.04.011
WU Wei-ming , HUANG Cheng-ke, WANG Jun, DAI Ge-xin, WANG Zeng-shou*. Effect of Rabeprazole on Steady-State Pharmacokinetics of Clopidogrel in Rats[J]. Chinese Pharmaceutical Journal, 2013, 48(4): 289-292 https://doi.org/10.11669/cpj.2013.04.011

参考文献

clopidogrel| rabeprazol| omeprazole| SR26334| pharmacokinetics| drug-interaction

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