N1-羧酰-5-氟尿嘧啶系列前体药物的体外降解动力学研究  

Studies on Degradation Kinetics of Various N_1-Acyl Derivatives of 5-Fluorouracil in vitro

作　　者：刘文胜[1] 罗维早[1] 张志荣[1] 

机构地区：[1]四川大学药学院,四川成都610041

出　　处：《中国医药工业杂志》2002年第9期434-439,共6页Chinese Journal of Pharmaceuticals

基　　金：国家杰出青年科学基金资助项目 (3 992 5 0 3 9)

摘　　要：采用 HPL C法测定 N1 -羧酰 - 5 -氟尿嘧啶系列前体药物在不同 p H磷酸盐缓冲溶液中、不同的组织匀浆中的含量以考察降解情况 ,并数学拟合求取降解动力学方程。同时对光敏感的 N1 -维甲酰 - 5 -氟尿嘧啶进行了光解动力学研究 ,还测定了该系列前体药物在正辛醇 -水两相中的分配系数。结果表明各前体药物在缓冲溶液和组织匀浆中的降解均为表观一级反应 ,光解动力学方程为对数曲线 ,前体药物的分配系数均高于 5 -氟尿嘧啶。其中 N1 -维甲酰- 5 -氟尿嘧啶和 N1 -山梨酰 - 5 -氟尿嘧啶的药物稳定性较好。Concentrations of five N 1 acyl derivatives of 5 fluorouracil in various pH buffer solutions and biological medias were determined by HPLC, which deduced the degradation kinetics functions and partition coefficients. The results showed degradations of these prodrugs displayed pseudofirst order kinetics in buffer solutions and biological medias, photolysis reactions were shown logarithm functions. The partition coefficient of the prodrugs was larger than that of 5 fluorouracil. Among them N 1 retinoyl 5 fluorouracil and N 1 sorbyl 5 fluorouracil had the potential to be prodrugs of 5 fluorouracil.

关 键 词：N1-羧酰-5-氟尿嘧啶系列 前体药物 体外降解动力学 研究 5-氟尿嘧啶 血脑屏障 HPLC 抗肿瘤药 

分 类 号：R979.1[医药卫生—药品] R961[医药卫生—药学]