氟尿嘧啶-聚酰胺-胺复合物的制备及大鼠体内药代动力学  

Preparation of fluorouracil-polyamidoamine complex and its pharmacokinetics in rats

作　　者：乔宏志[1] 李娟[1] 王洋[1] 李强[1] 

机构地区：[1]中国药科大学药剂学教研室,南京210009

出　　处：《中国药科大学学报》2011年第6期510-515,共6页Journal of China Pharmaceutical University

基　　金：国家"重大新药创制"科技重大专项资助项目(No.2009ZX09310-004);中央高校基本科研业务费专项资金资助项目(No.JKY2009039)~~

摘　　要：合成并表征了聚酰胺-胺(PAMAM)G5.0树枝状聚合物,平衡透析法制备氟尿嘧啶-聚酰胺-胺复合物(5-Fu-PAMAM),研究PAMAM对5-Fu的结合能力;高效液相色谱法研究大鼠经口给予5-Fu混悬液和5-Fu-PAMAM复合物的药代动力学。结果显示,当5-Fu与PAMAM G5.0的物质的量比在250附近达到最大结合,制备的复合物粒径为(30.2±4.9)nm。大鼠经口给予复合物组的Ka,cmax均较混悬液组有显著增加(P<0.01),AUC0-∞是混悬液组的1.37倍。研究表明PAMAM能显著增加5-Fu的口服吸收,提高5-Fu制剂的生物利用度。Polyamidoamine（PAMAM） G5.0 dendrimers were synthesized and characterized.The complex of PAMAM with fluorouracil（5-Fu） was prepared by equilibrium dialysis,and the binding capacity of PAMAM to 5-Fu was studied.The pharmacokinetics in rats receiving oral dosing of 5-Fu suspension and complex were investigated by HPLC.The maximum combination of complex occurred when molar ratio of 5-Fu and PAMAM G5.0 was about 250.The average size of complex was（30.2±4.9） nm.Oral pharmacokinetics in rats showed that the Ka,cmax of the complex had a significant increase（P0.01）,and AUC0-∞ was 1.37 times to that of the suspension group.These results indicated that PAMAM can increase the absorption of 5-Fu significantly and improve its oral bioavailability.

关 键 词：聚酰胺-胺 树状聚合物 氟尿嘧啶 药代动力学 

分 类 号：R944[医药卫生—药剂学] R969.1[医药卫生—药学]