【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。更多还原

【Abstract】 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 concentration-time curve in plasma of rats and tissue distribution of rHDL-ACM after iv administration. Results With AlCl₃ 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.更多还原