静脉注射盐酸伊立替康纳米粒后代谢物7-乙基-10-羟基喜树碱的药动学和组织分布研究  

Pharmacokinetics of SN-38 in rats and tissue distribution of 7-ethyl-10-hydroxycamptothecin in mice after intravenous injection of irinotecan hydrochloride nanoparticles

作　　者：杨付英[1] 张文萍[1,2] 王欣瑜[1,2] 杨文成[3] 党宏万[4,1,2] 

机构地区：[1]宁夏医科大学总医院药剂科,宁夏银川750004 [2]宁夏医科大学总医院临床药理研究室,宁夏银川750004 [3]宁夏医科大学药学院,宁夏银川750004 [4]宁夏医科大学总医院肿瘤医院药剂科,宁夏银川750004

出　　处：《药学学报》2014年第7期1029-1033,共5页Acta Pharmaceutica Sinica

基　　金：宁夏自然科学基金资助项目(NZ13171)

摘　　要：考察大鼠和小鼠尾静脉注射盐酸伊立替康纳米粒(CPT-11 NPs)后7-乙基-10-羟基喜树碱(SN-38)的药动学和组织分布特性。LC-MS/MS法测定生物样品中SN-38的含量,比较尾静脉注射CPT-11 NPs和CPT-11溶液后代谢物SN-38在大鼠体内的药动学与小鼠的组织分布特点。在药动学研究中,与CPT-11溶液相比,纳米粒组中SN-38的t1/2由2.17 h延长到2.67 h,AUC与溶液相比无变化;在组织分布研究中,与溶液组相比,纳米粒组中的代谢物SN-38随着时间的延长,其在小鼠血液、结肠及肺中的药量显著提高,其次是肝和脾,心与脑无变化,肾脏中的药量随时间的延长反而减少。CPT-11 NPs能延长代谢物SN-38的体内循环时间,显著增加小鼠血液、结肠及肺组织中的药物含量,将前药盐酸伊立替康制备为纳米粒使代谢物有结肠和肺部靶向性。The paper reported an investigation of the pharmacokinetics of SN-38（7-ethyl-10-hydroxycamptothecin） in rats and the tissue distribution in mice after injection of irinotecan hydrochloride nanoparticles（CPT-11） via tail veins. An LC-MS/MS method was established to determine the concentrations of SN-38 in whole blood of rats and in different tissues of mice. The pharmacokinetics and tissue distribution of SN-38 were compared after the intravenous injection of CPT-11 NPs and CPT-11 solution. Compared with irinotecan solution, the elimination half-life of SN-38 was prolonged from 2.17 h to 2.67 h after the intravenous injection of CPT-11 NPs, but its AUC had little change. After the injection of CPT-11 NPs in mice, over time, the concentrations of CPT-11-metabolized SN-38 in CPT-11 NPs were significantly higher in the whole blood, colon and lungs than those in CPT-11 solution, followed by in the spleen and liver, but those in the heart and brain had no change. However, the amount of SN-38 in the kidneys was reduced with time. CPT-11 NPs could prolong SN-38＇s（one of its metabolites） blood circulation time in rats and significantly increased the concentration of CPT-11-metabolized SN-38 in the whole blood, colon and lungs of mice. CPT-11 NPs made SN-38 efficiently target-bind to the colon and lungs of mice.

关 键 词：盐酸伊立替康纳米粒 LC-MS MS 药动学 组织分布 

分 类 号：R945[医药卫生—微生物与生化药学]