普朗尼克抑制P-糖蛋白药泵的作用  

The inhibitory effect of Pluronic on P-glycoprotein drug pump

作　　者：黄建耿[1] 斯陆勤[1] 左克源[1] 吴祥根[1] 裘军[1] 李高[1] 

机构地区：[1]华中科技大学同济医学院药学院,湖北武汉430030

出　　处：《药学学报》2007年第9期989-994,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30572265);湖北省卫生厅科研基金项目(JX2B04).

摘　　要：采用Caco-2细胞和动物模型,以维拉帕米为阳性对照,考察普朗尼克对塞利洛尔在Caco-2单层膜与肠道黏膜吸收的影响。用高效液相色谱法检测药物浓度,计算表观透过系数、吸收速率常数与有效透过系数等参数,评价普朗尼克对P-糖蛋白药泵的抑制作用。结果显示,塞利洛尔Caco-2细胞膜转运基底端(BL)到顶端(AP)的透过系数Papp大于AP到BL的Papp,分别为(2.10±0.13)×10-6和(0.333±0.018)×10-6cm.s-1,且双向转运受到抑制剂维拉帕米和普朗尼克的影响。大鼠在体肠灌流实验中塞利洛尔在十二指肠段、空肠、回肠与结肠段的吸收速率常数ka分别为(0.09±0.03),(0.14±0.04),(0.11±0.03)与(0.05±0.02)h-1;合用维拉帕米后各肠段吸收速率常数ka分别为(0.14±0.03),(0.24±0.02),(0.25±0.03)和(0.23±0.02)h-1;合用普朗尼克后各肠段吸收速率常数ka分别为(0.13±0.02),(0.22±0.02),(0.22±0.03)和(0.20±0.03)h-1。可见,普朗尼克通过抑制P-gp外排作用,促进塞利洛尔Caco-2细胞膜和大鼠肠道黏膜的吸收。To investigate the inhibitory effect of Pluronic on P-glycoprotein （P-gp） drug efflux pump, Caco-2 cells and animal models were established to study the influence of Pluronic on celiprolol transport across Caco-2 cell monolayer and intestinal mucous membrane with verapamil set as a positive control. Drug concentration was measured by HPLC and the apparent permeability coefficient （Papp） , absorption rate constant （ko） and the effective permeability coefficient （Poll） were calculated. Papp of basolateral to apical side and apical to basolateral side was （2.10 ± 0. 13） ×10^-6 and （0.333 ± 0.018） ×10^-6 cm·s^-1 , respectively. Transports of celiprolol across Caco-2 cell monolayer were influenced by both verapamil and Pluronic. The absorption constants （k,） of celiprolol at duodenum, jejunum, ileum, and colon were （0.09±0.03）, （0.14±0.04）, （0.11 ±0.03） and （0.05 ±0.02） h^-1, ka of celiprolol in verapamilgroup were （0.14±0.03）, （0.24±0.02）, （0.25 ±0.03） and （0.23 ±0.02） h^-1, and ka of celiprolol in Pluronic group were（0. 13 ±0.02）, （0.22 ±0. 02）, （0.22 ±0.03） and （0.20 ±0.03） h^-1, respectively. Pluronic showed significant effect on inhibiting P-gp of Caco-2 cell and intestinal mucosa in rats.

关 键 词：CACO-2细胞模型 P-糖蛋白 在体肠灌流 塞利洛尔 普朗尼克 

分 类 号：R943.4[医药卫生—药剂学]