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Aim:To study the pharmacokinetics and tissue distribution of 5-fluorouracil en-capsulated by galactosylceramide liposomes(5-Fu-GCL)in mice.Methods:Theconcentration of 5-fluorouracil(5-Fu)in serum was detected by high performanceliquid 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-timeprofile of the two preparations in the liver were studied.Data were analyzed by3p97 program.Results:Serum concentration-time curves of 5-Fu-GCL and free5-Fu conformed to one compartment model of first order absorption.5-Fu-GCLat 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 of24.9±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 hadT_(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).Thetissue distribution of 5-Fu-GCL in the liver and immune organs was significantlyincreased,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:Thepharmacokinetics and tissue distribution of 5-Fu-GCL appears to be linear-re-lated and dose-dependent,and exhibits sustained-release and hepatic targetcharacteristics.
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-GCL (80,40,20 mg / kg) and free 5-Fu (40 mg / kg) were injected intravenously into mice. The tissue distribution of 5- (40 mg / kg) was investigated, and concentration-time profile of the two preparations in the liver were studied. Data were analyzed by 3 p97 program. Results: Serum concentration-time curves of 5-Fu-GCL and free5-Fu conformed to one compartment model of first order absorption.5-Fu-GCLat 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. Contrast 5-Fu at 40 kg / mg hadT_ (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 .Thetissue dist ribution 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 : Thepharmacokinetics and tissue distribution of 5-Fu-GCL appears to be linear-re-lated and dose-dependent, and and exhibits sustained-release and hepatic target characteristics.