大鼠肠道对左旋延胡索乙素及其消旋体的吸收差异研究  

Difference absorption of l-tetrahydropalmatine and dl-tetrahydropalmatine in intestine of rats

作　　者：吴佩盛[1] 黄善定[2] 叶亚菊 孙思源[1] 蒋惠娣[1] 

机构地区：[1]浙江大学药学院,浙江杭州310058 [2]宁波大学第三附属医院,浙江宁波315020 [3]鄞州人民医院,浙江宁波315040

出　　处：《药学学报》2007年第5期534-537,共4页Acta Pharmaceutica Sinica

基　　金：宁波市科技局资助项目(2006C100017).

摘　　要：考察延胡索乙素(THP)的吸收机制,并研究其消旋体与左旋延胡索乙素(l-THP)在大鼠肠道的吸收差异。应用单向灌流模型,采用HPLC法测定THP及l-THP在灌流液中的浓度变化。灌流液中THP质量浓度为8,16,32μg.mL-1时,THP吸收速率常数和有效吸收系数均无统计差异(P>0.05),各肠段的吸收速率常数和有效吸收系数也无统计差异(P>0.05);l-THP和THP在大鼠肠道吸收存在显著性差异(P<0.05);在肠道灌流液中加入P-糖蛋白(P-gp)抑制剂维拉帕米后,THP吸收显著增加,而l-THP吸收几乎不变。THP在肠黏膜的转运为被动扩散过程,无特殊吸收窗口;THP消旋体与l-THP的吸收差异可能与P-gp与右旋THP的选择性结合有关。To investigate the difference in absorptive of tetrahydropalmatine （ THP ） and l-tetrahydropalmatine （l-THP） in rat intestine as well as the mechanism of the absorption of THP, in situ single pass perfusion model was used and the concentration of THP in perfusate was determined by HPLC. The absorption rate constant （ka ） and effective permeability values （Peff） of THP had no significant difference （P 〉 0. 05） at concentration of 8, 16 and 32 μg·mL^-1 in perfusion or in four different regions of intestine of rat （duodenum, jejunum, ileum, colon）. The absorption of l-THP and THP in jejunum had significant difference （P 〈 0. 05）. The k and P41 of THP increased obviously when verapamil was coperfused with THP, while those of l-THP were not influenced by verapamil. The absorption of THP in intestine showed the passive diffusion process, and without a special absorption region. The stereoselective absorption difference may result from stereoselective combination of P-glycoprotein with d-THP.

关 键 词：延胡索乙素 左旋延胡索乙素 在体肠单向灌流模型 吸收 

分 类 号：R917[医药卫生—药物分析学]