Pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated by galactosylceramide liposomes in mice  

作　　者：YongJIN JunLI Long-fuRONG Xiong-wenLü YanHUANG Shu-yunXU 

机构地区：[1]InstituteofClinicalPharmacology,SchoolofPharmacy,AnhuiMedicalUniversity,Hefei230032,China

出　　处：《Acta Pharmacologica Sinica》2005年第2期250-256,共7页中国药理学报（英文版）

基　　金：Project supported by Key Teacher Foundation of Ministry of Education of China(№ 1869);Young Teacher Foundation of Department of Education of Anhui Province(№ 2000jg112)

摘　　要：Aim:To study the pharmacokinetics and tissue distribution of 5-fluorouracil en- capsulated by galactosylceramide liposomes(5-Fu-GCL)in mice.Methods:The concentration of 5-fluorouracil(5-Fu)in serum was detected by high performance liquid chromatography after 5-Fu-GCL(80,40,20 mg/kg)and free 5-Fu(40mg/ kg)were injected intravenously into mice.The tissue distribution of 5-Fu-GCL (40mg/kg)and free 5-Fu(40mg/kg)was investigated,and concentration-time profile of the two preparations in the liver were studied.Data were analyzed by 3p97 program.Results:Serum concentration-time curves of 5-Fu-GCL and free 5-Fu conformed to one compartment model of first order absorption.5-Fu-GCL at 80,40,and 20 mg/kg had T_(1/2Ke)of 25.8±4.2,27.3±4.4,and 28.2±5.6 min;C_0 of 24.9±4.9,17.7±3.6,and 11.5±2.7 mg/L;and AUC of 990.0±45.2,622.5±38.3, and 340.4±25.6 mg.min.L^(-1),respectively.In contrast free 5-Fu at 40 kg/mg had T_(1/2Ke)of 15.8±2.2min,C_0 of 35.8±6.2mg/L,AUC of 639.0±35.9 mg.min.L^(-1).The tissue distribution of 5-Fu-GCL in the liver and immune organs was significantly increased,while in heart and kidney it was remarkably decreased.The AUC of 5- Fu-GCL in the liver was 3 times higher than that of free 5-Fu.Conclusion:The pharmacokinetics and tissue distribution of 5-Fu-GCL appears to be linear-re- lated and dose-dependent,and exhibits sustained-release and hepatic target characteristics.Aim:To study the pharmacokinetics and tissue distribution of 5-fluorouracil en- capsulated by galactosylceramide liposomes(5-Fu-GCL)in mice.Methods:The concentration of 5-fluorouracil(5-Fu)in serum was detected by high performance liquid chromatography after 5-Fu-GCL(80,40,20 mg/kg)and free 5-Fu(40mg/ kg)were injected intravenously into mice.The tissue distribution of 5-Fu-GCL (40mg/kg)and free 5-Fu(40mg/kg)was investigated,and concentration-time profile of the two preparations in the liver were studied.Data were analyzed by 3p97 program.Results:Serum concentration-time curves of 5-Fu-GCL and free 5-Fu conformed to one compartment model of first order absorption.5-Fu-GCL at 80,40,and 20 mg/kg had T_(1/2Ke)of 25.8±4.2,27.3±4.4,and 28.2±5.6 min;C_0 of 24.9±4.9,17.7±3.6,and 11.5±2.7 mg/L;and AUC of 990.0±45.2,622.5±38.3, and 340.4±25.6 mg.min.L^(-1),respectively.In contrast free 5-Fu at 40 kg/mg had T_(1/2Ke)of 15.8±2.2min,C_0 of 35.8±6.2mg/L,AUC of 639.0±35.9 mg.min.L^(-1).The tissue distribution of 5-Fu-GCL in the liver and immune organs was significantly increased,while in heart and kidney it was remarkably decreased.The AUC of 5- Fu-GCL in the liver was 3 times higher than that of free 5-Fu.Conclusion:The pharmacokinetics and tissue distribution of 5-Fu-GCL appears to be linear-re- lated and dose-dependent,and exhibits sustained-release and hepatic target characteristics.

关 键 词：5-FLUOROURACIL GALACTOSYLCERAMIDE liposomes pharmacokinetics 

分 类 号：R979.1[医药卫生—药品] R969.1[医药卫生—药学]