肠道P-糖蛋白辅料抑制剂的研究进展  

Advances in the study of excipient inhibitors of intestinal P-glycoprotein

作　　者：闫方[1] 斯陆勤[1] 黄建耿[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》2008年第11期1071-1076,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30572265)

摘　　要：位于小肠上皮细胞顶端的P-糖蛋白(P-gp)是一种能量依赖性外排泵,可降低多种底物药物的生物利用度。抑制肠道P-gp以增加药物生物利用度受到越来越多的关注。本文将肠道P-gp辅料抑制剂分为非离子型表面活性剂、聚乙二醇类、β-环糊精衍生物和壳聚糖硫醇盐,并对其作用机制进行综述。与传统P-gp抑制剂相比,辅料抑制剂的非特异性药理作用极小,因此几乎不产生副作用。辅料抑制剂有望代替传统P-gp抑制剂,广泛用于增加难溶性及低口服吸收药物的肠道吸收,从而增加该类药物的生物利用度。这些辅料抑制P-gp的机制及其临床应用还需更多研究和探讨。P-glycoprotein （P-gp） located in the apicalmembranes of intestinal absorptive cells is an energy-dependent efflux pump which can reduce the bioavailability of a wide range of substrate drugs. There is increasingly interest in enhancing the bioavailability of these molecules by inhibiting intestinal P-gp. A classification of excipient inhibitors of intestinal P-gp nonionic surfactants, poly （ ethylene glycol）, derivates of fl-cyclodextrin and thiolated chitosan will be presented and then the inhibition mechanism will be discussed. Compared with traditional P-gp inhibitor, excipient inhibitors appear to have minimal nonspecific pharmacological activity, thus potential side effects can be mostly avoided. These excipient inhibitors, which hold the promise of replacing the traditional ones, will be extensively employed to significantly improve the intestinal absorption of poorly soluble and absorbed drugs as a result of P-gp inhibition, and thus to enhance the bioavailability of these drugs. However, the further studies of both the mechanism and clinical application are urgently needed.

关 键 词：P-糖蛋白 药用辅料 抑制剂 

分 类 号：R943[医药卫生—药剂学]