盐酸伊立替康脂质体临床前药代动力学、耐受性和药效学研究  

Preclinical pharmacokinetics,tolerance and efficacy of irinotecan hydrochloride liposomes

作　　者：郑庆梅 韩景宾 宫新江 杨焕一 杨光丽 杨清敏 严守升 王晶翼 

机构地区：[1]齐鲁制药有限公司药物研究院,济南250100 [2]山东省注射用微粒给药新技术重点实验室,济南250100

出　　处：《中国新药杂志》2012年第14期1591-1595,共5页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项(2011ZX09401-015);"泰山学者"建设工程专项(2009年)

摘　　要：目的:研究盐酸伊立替康脂质体与盐酸伊立替康注射液相比,在药代动力学、毒理学和药效方面的改善程度。方法:考察盐酸伊立替康注射液和盐酸伊立替康脂质体分别以1 mg·kg-1经静脉给药在Beagle犬体内的药代动力学;经静脉注射给药对昆明小鼠的最大耐受量(MTD);对裸鼠皮下接种人结肠癌HT-29、人胃癌NCI-N87移植瘤的抑制作用,通过各组药代动力学参数、MTD和相对肿瘤体积的动态变化比较其改善程度。结果:盐酸伊立替康注射液和脂质体在犬体内的t1/2分别为1.50和9.83 h;脂质体的AUC0～t为注射液的95倍;MTD分别为80和160 mg·kg-1;对HT-29和NCI-N87移植瘤模型的最高抑制率分别为54.2%,97.3%和55.4%,98.5%,且给予5 mg·kg-1脂质体的疗效与50 mg·kg-1注射液相当。结论:盐酸伊立替康脂质体在药代动力学、毒理学和对HT-29,NCI-N87的疗效方面明显优于注射液。Objective：To determine the improvement in pharmacokinetics, toxicity and antitumor effect of irinotecan hydrochloride liposomes compared with irinotecan hydrochloride injection. Methods： The pharmacokinetics of the two preparations was investigate in beagle dogs at dose of 1 mg· kg^-1 after intravenous administration; the MTDs in KM mice was determined after intravenous administration; the antitumor effects against human colon cancer HT-29 and gastric cancer NCI-N87 xenografts were measured. The improvement of irinotecan hydrochloride liposomes to the injection was evaluated by comparing the pharmacokinetic parameters, MTDs and tumor growth- curves. Results：The tl/2 were 1.50, 9.83 h for the liposomes and injection, respectively, and the AUC0., of irinotecan hydrochloride liposomes was 95 times of that of the injection. The MTDs were 80, 160 mg· kg^-1 for the liposomes and injection, respectively. The maximum relative tumor volume inhibition ratios for HT-29 and NCI-N87 were 54.2% and 55.4% for irinotecan hydrochloride injection and 97.3% and 98.5% for the liposomes, and irinotecan hydrochloride liposomes at dose of 5 mg· kg^-1 had comparable efficacy with irinotecan hydrochloride injection at dose of 50 mg· kg^-1. Conclusion ： Irinotecan hydrochloride liposomes are significantly better than the injection in pharmacokinetics, toxicity and antitumor effect.

关 键 词：盐酸伊立替康 脂质体 结直肠癌 胃癌 肿瘤抑制率 毒性 药代动力学 

分 类 号：R96[医药卫生—药理学] R979.1[医药卫生—药学]