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

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K_a，c_max均较混悬液组有显著增加（P<0.01），AUC_0-∞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。

Abstract: 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 K_a,c_max of the complex had a significant increase (P<0.01),and AUC_0-∞ 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.