半乳糖神经酰胺脂质体包裹的5-氟尿嘧啶在小鼠体内的药代动力学及组织分布

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

作者信息

Jin Yong, Li Jun, Rong Long-Fu, Lü Xiong-Wen, Huang Yan, Xu Shu-Yun

机构信息

Institute of Clinical Pharmacology, School of Pharmacy, Anhui Medical University, Hefei 230032, China.

出版信息

Acta Pharmacol Sin. 2005 Feb;26(2):250-6. doi: 10.1111/j.1745-7254.2005.00530.x.

DOI:10.1111/j.1745-7254.2005.00530.x

PMID:15663907

Abstract

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 x min x 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 x min x 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.

摘要

目的

研究半乳糖神经酰胺脂质体包裹的5-氟尿嘧啶（5-Fu-GCL）在小鼠体内的药代动力学及组织分布。

方法

将5-Fu-GCL（80、40、20mg/kg）和游离5-氟尿嘧啶（5-Fu，40mg/kg）静脉注射入小鼠体内后，采用高效液相色谱法检测血清中5-氟尿嘧啶（5-Fu）的浓度。考察5-Fu-GCL（40mg/kg）和游离5-Fu（40mg/kg）的组织分布情况，并研究两种制剂在肝脏中的浓度-时间曲线。数据采用3p97程序进行分析。

结果

5-Fu-GCL和游离5-Fu的血清浓度-时间曲线均符合一级吸收单室模型。80、40和20mg/kg的5-Fu-GCL的T(1/2Ke)分别为25.8±4.2、27.3±4.4和28.2±5.6分钟；C0分别为24.9±4.9、17.7±3.6和11.5±2.7mg/L；AUC分别为990.0±45.2、622.5±38.3和340.4±25.6mg·min·L(-1)。相比之下，40mg/kg的游离5-Fu的T(1/2Ke)为15.8±2.2分钟，C0为35.8±6.2mg/L，AUC为639.0±35.9mg·min·L(-1)。5-Fu-GCL在肝脏和免疫器官中的组织分布显著增加，而在心脏和肾脏中则显著减少。5-Fu-GCL在肝脏中的AUC比游离5-Fu高3倍。