肝靶向药物EVk在大鼠组织中的分布研究

The preliminary study of tissue distribution of liver-targeted drug EVk in rats

目的研究合成表阿霉素与Vk3的偶联物(EVk)的组织分布情况。方法经同位素示踪法和HPLC法观察EVk在动物组织中的分布。结果同位素示踪法中,肝脏有一过性浓集现像,但未见特异性高药物浓度分布。结合HPLC检测到保留时间1.9、5.1 min处有两个较高的未知吸收峰,推测未知吸收峰应为EVk的肝代谢产物,肝组织较其他组织有较高的代谢物浓度。结论 EVk原药在肝脏及其他组织中的分布浓度低,但其代谢产物浓度较高,可能通过快速肝代谢进而通过代谢物在肝脏发挥靶向治疗作用。

OBJECTIVE To observe the tissue distribution of the drug conjugated of epirubicin and Vk3.METHODS HPLC and isotope tracer method were used to observe the distribution in animal tissues.RESULTS Isotope tracer method showed that there was a imaging of a transient high concentration of 131iodine but no specific distribution of high drug concentration in liver.According to the phenomenon that there were two unknown high peaks at tR=1.8 min and 5.1 min in HPLC,we should speculate that unknown peaks should be metabolites of EVk.The study showed higher concentrations of metabolites in liver than in the other tissues.CONCLUSION The original concentrations of EVk in different tissues were low,but the concentrations of EVk metabolites were relatively high in these tissues,which indicated that there might be a possibility that EVk may play a role in targeting therapy by metabolites produced in rapid liver metabolism.