延胡索乙素的大鼠在体肠吸收与立体选择性特征研究  

Studies on Intestinal Absorption Characteristics of Tetrahydropalmatine in Rats

作　　者：洪战英[1] 范国荣[1] 柴逸峰[1] 闻俊[1] 殷学平[1] 吴玉田[1] 

机构地区：[1]中国人民解放军第二军医大学药学院

出　　处：《中国药学杂志》2007年第14期1104-1107,共4页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(30271603)

摘　　要：目的研究延胡索乙素在大鼠小肠段的吸收动力学特征和立体选择性特征。方法采用大鼠在体小肠灌流实验和在体分离肠袢实验,应用紫外分光光度法和HPLC分别测定酚红和延胡索乙素的含量,手性固定相拆分法测定延胡索乙素对映体的峰面积比值。结果延胡索乙素在不同药物质量浓度10,25,50mg·L-1时,肠吸收速率常数Ka分别为0.403,0.461,0.402h-1;不同pH值4.5,6.5,8.0时Ka分别为0.353,0.458,0.409h-1;在体动物实验测得延胡索乙素对映体间的峰面积比值均接近0.5∶0.5。结论不同的药物浓度和pH值对延胡索乙素在大鼠小肠的吸收无显著影响,药物的吸收呈一级动力学过程,吸收机制为被动扩散;延胡索乙素两对映体在体肠吸收没有差异,不存在立体选择性。OBJECTIVE To investigate the absorption kinetics and stereoselectivity of tetrabydropalmatine（THP） enantiomers in rat intestine. METHODS The in situ intestine recirculation and the intestinal loop experiments were performed in rats. The concentrations of phenolsulfonphthalen and THP were determined by validated UV-HPLC assay, respectively. The d-/l-THP enantiomers ratios in recirculation solutions and plasma samples from portal vein were obtained by chiral separation. RESULTS The absorption rate constants（Ka） at THP concentrations of 10,25 and 50 mg· L^-1 were 0. 403,0. 461 and 0. 402 h^ -1 ,respectively. Ka at pH of 4. 5,6. 5 and 8.0 were 0. 353,0. 458 and 0. 409 h^-1 ,respectively. The d-/l- ratios in recirculation solutions and plasma samples from portal vein remained as closely as 0. 5： 0.5. CONCLUSION The concentrations of THP and pH of drag solution had no significant effect on the absorption kinetics. The absorption of THP from intestine is mainly via passive transport mechanism and no stereoselectivity is displayed in the absorption of the enantiomers.

关 键 词：延胡索乙素 吸收速率常数 立体选择性 小肠 

分 类 号：R969[医药卫生—药理学]