肝靶向抗癌药半乳糖基拟糖白蛋白─米托蒽醌和米托蒽醌的药代动力学研究

目的：研究肝靶向抗癌药物半乳糖基拟糖白蛋白米托蒽醌（ＮＧＡＤＨＡＱ）的小鼠体内分布，及对ＮＧＡＤＨＡＱ和米托蒽醌（ＤＨＡＱ）在小鼠体内的药代动力学进行比较。方法：利用放射性核索示踪法及ＨＰＬＣ进行测定。结果：体内分布结果表明ＮＧＡＤＨＡＱ具有良好的趋肝性，５ｍｉｎ时肝摄取率为６５％左右，ＨＰＬＣ实验结果表明ＮＧＡＤＨＡＱ在血中有较好的稳定性，不易解离出ＤＨＡＱ。ＮＧＡＤＨＡＱ和ＤＨＡＱ在肝中的达峰时间分别为０．２和１０ｍｉｎ，两者在血中消除均较快，ＮＧＡＤＨＡＱ的峰浓度是ＤＨＡＱ的１．９倍，不同时间点ＮＧＡＤＨＡＱ的肝药浓度／血药浓度均比ＤＨＡＱ的大。结论：ＮＧＡＤＨＡＱ浓集肝脏速度快，具肝靶向分布特征。

Study of pharmacokinetics of liver targetting antineoplastic agent neoglycoalbuminmitoxantrone and mitoxantrone in mice

BJECTIVE: The biodistribution of hepatic targetting antineoplastic agent,galactosyl neoglycoalbuminmitoxantrone conjugate (NGADHAQ) was assessed by a radioactive tracer technique in mice. METHODS:WTBZThe pharmacokinetics study of NGADHAQ and DHAQ in mice liver and plasma in vivo were also carried out comparatively by a HPLC method. RESULTS: The biodistribution of NGADHAQ showed a good liver targetting tendency with (65.454.28)% of total given radio quantity at 5min.The data of pharmacokinetic study indicated that the tmax of NGADHAQ and DHAQ in liver were 0.2 and 10.0 min,and the peak concentration of DHAQ in NGADHAQ group was 1.9 times larger than that in DHAQ group (same DHAQ dosage).NGADHAQ in blood was stable.The proportion of cliver to cblood of each time was used to evaluate the targetting tendency of NGADHAQ and DHAQ with larger of NGADHAQ. CONCLUSION: The reaching speed to liver of NGADHAQ was fast,and it showed a pretty good liver targetting tendency.