大鼠口服硫酸氢氯吡格雷的多晶型吸收特点研究
Absorption dynamic characteristics of clopidogrel bisulfate polymorphs in rat
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摘要:
本文采用多种分析检测技术对硫酸氢氯吡格雷的4种晶型物质进行了表征, 并采用高效液相色谱 (high performance liquid chromatogram, HPLC) 技术测定大鼠血浆中硫酸氢氯吡格雷及其代谢产物的含量, 研究了大鼠口服硫酸氢氯吡格雷4种不同晶型的吸收特点。结果显示大鼠灌胃给予硫酸氢氯吡格雷后血浆中可以检测到反应吸收过程的代谢产物, 硫酸氢氯吡格雷4种晶型的代谢产物曲线下面积有显著性差异。故认为硫酸氢氯吡格雷的不同晶型物质表现出不同的药代动力学特征, 提示晶型物质状态不同可能会影响药物的体内作用。
Abstract:Four crystalline forms of clopidogrel bisulfate were characterized by analytical techniques. Aiming to research the absorption characteristics of clopidogrel bisulfate polymorphs after taken orally by rat, and to estimate the influence of crystal form to pharmacodynamic action, four crystalline forms of clopidogrel bisulfate were administered intragastrically to rats, and high performance liquid chromatography (HPLC) was used to measure the contents of clopidogrel bisulfate and its metabolite in rat plasma. The metabolite of clopidogrel bisulfate was detected in rat plasma. There were significant deviations among four crystalline forms in the areas under curve of the metabolite of clopidogrel bisulfate. We concluded that the different crystal forms of clopidogrel bisulfate showed different pharmacokinetic characteristics, which might affect pharmacodynamic action.
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