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

摘要

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_( 1/2 ke ) 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_( 1/2 ke ) of 15.8 +- 2.2 min, C_0 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.