Acta Pharmacologica Sinica 2005 February; 26 (2): 250-256; doi: 10.1111/j.1745-7254.2005.00530.x

Aim: To study the pharmacokinetics and tissue distribution of 5-fluorouracil encapsulated 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 (40 mg/kg) were injected intravenously into mice. The tissue distribution of 5-Fu-GCL (40 mg/kg) and free 5-Fu (40 mg/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; C₀ 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±2.2 min, C₀ of 35.8±6.2 mg/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-related and dose-dependent, and exhibits sustained-release and hepatic target characteristics.

Keywords: 5-fluorouracil; galactosylceramide; liposomes; pharmacokinetics