Open AccessPharmacokinetics and tissue distribution of 5‐fluorouracil encapsulated by galactosylceramide liposomes in mice 1
Author(s) -
JIN Yong,
LI Jun,
RONG Longfu,
LÜ Xiongwen,
HUANG Yan,
XU Shuyun
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00530.x
Subject(s) - pharmacokinetics , fluorouracil , tissue distribution , liposome , distribution (mathematics) , pharmacology , chemistry , medicine , biochemistry , chemotherapy , mathematical analysis , mathematics
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; 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±2.2 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.