重组高密度脂蛋白-阿克拉霉素大鼠体内血液动力学及组织分布  

Pharmacokinetics and tissue distribution of recombinant complex of HDL and aclarcinomycin in rats

作　　者：楼滨[1] 董继斌[1] 吴满平[1] 

机构地区：[1]复旦大学药学院生物化学教研室,上海200032

出　　处：《复旦学报（医学版）》2006年第5期626-630,共5页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金项目(39770164)资助

摘　　要：目的研究重组高密度脂蛋白-阿克拉霉素(rHDL-ACM)静脉注射给药后在大鼠体内的血液动力学及组织分布,为肝癌靶向治疗寻找新的途径。方法建立荧光法测定血浆和组织匀浆中rHDL-ACM浓度方法,测定不同时相大鼠血浆或组织匀浆中rHDL-ACM浓度。结果加入AlCl3作为荧光增强剂,ACM的激发波长为441 nm,发射波长为505 nm。该方法测定rHDL-ACM在大鼠血浆中高中低3种浓度的平均回收率>84.5%。肝的平均回收率为85.1%,肾的平均回收率为78.2%,脾的平均回收率为86.3%,肺的平均回收率为84.4%。rHDL-ACM在血浆中消除半衰期比fACM消除半衰期延长近一倍。注射rHDL-ACM 4 h后,脾和肺中药物浓度下降迅速,药物显著浓集于肝脏。结论注射后rHDL-ACM在大鼠肝脏中累积,提示该药具有肝脏靶向作用。Purpose To evaluate the pharmacokinetics and distribution of rHDL-ACM in rats after intravenous administration and explore the possibility of HDL-ACM complex in hepatoma chemotherapy. Methods Fluorescence spectrophotometry was established for determination of rHDL-ACM concentration in plasma and tissues of rats, then it was applied to determine rHDL-ACM concentrationtime curve in plasma of rats and tissue distribution of rHDL-ACM after iv administration. Results With A1C13 as fluorescence intensifying agent, ACM was detected at λex 441 nm, λem 505 nm. The average recoveries of rHDL-ACM from plasm were 84. 5%, recoveries of rHDL-ACM from the liver, kidney,spleen and lung were 85. 1%, 78. 2%, 86.3%, 84.4% respectively. The half life of rHDL-ACM was longer about one times than free ACM（fACM）. The concentration of rHDL-ACM in the spleens and lungs of rats were decreased and rHDL-ACM was accumulated in livers significantly after iv injection for four hours. Conclusions The rHDL-ACM was mostly accumulated by livers after iv administration and The complex of ACM with the hepatotropic carrier HDL indeed enhances its liver uptake.

关 键 词：高密度脂蛋白 血液动力学 组织分布 

分 类 号：R969.1[医药卫生—药理学]