双靶向配体化力达霉素在大鼠体内药动学及组织分布和排泄  

Distribution, excretion and pharmacokinetic research of dual target ligand-based lidamycin in rats

作　　者：叶程[1] 曹睿[1] 宋文凭 张玉民[2] 樊慧蓉[2] 刘鉴峰[2] 李亮[1] 邵荣光[1] YE Cheng;CAO Rui;SONG Wen-ping;ZHANG Yu-min;FAN Hui-rong;LIU Jian-feng;LI Liang;SHAO Rong-guang(Institute of Medical Biotechnology,Chinese Academy of Medical Sciences,Beijing 100050,China;Institute of Radiation Medicine Chinese Academy of Medical Sciences,Tianjin 300192,China)

机构地区：[1]中国医学科学院医药生物技术研究所,北京100050 [2]中国医学科学院放射医学研究所,天津300192

出　　处：《中国药理学与毒理学杂志》2019年第8期595-600,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技重大专项（2014ZX09201042-002）;国家自然科学基金（81472787）;中国医学科学院医学与健康科技创新工程项目协同创新团队项目（2016-I2M-3-013）~~

摘　　要：目的研究双靶向配体化力达霉素(DTLL)在大鼠体内的药动学特征及组织分布和排泄。方法单次iv给予Wistar大鼠[125I]DTLL,给药剂量为2625 kBq·0.05 mg-1·kg-1。分别收集0~6 h内组织样本、0~24 h内血清样本以及0~168 h内尿液、粪便和胆汁样本,用液体闪烁仪分别检测样品放射性浓度,用WinNonlin软件和非房室模型统计矩法计算药动学参数,并分析[125I]DTLL在体内的分布和排泄。结果DTLL原型药物的曲线下面积(AUC0-∞)为(184±33)h·μg·L-1,半衰期(t1/2)为(3.98±0.75)h,清除率(Cl)为(278±41)mL·h-1·kg-1。[125I]DTLL iv给予大鼠后,广泛分布于全身各组织中,在主要脏器中均未发现蓄积现象;给药后0~168 h,粪便和尿液累积排泄分数分别为(10.4±6.6)%和(82.5±2.6)%,经粪尿总排泄量可达给药剂量的(92.9±7.4)%。结论DTLL iv给予健康Wistar大鼠后可迅速分布于全身,可能不能通过血脑屏障,DTLL主要通过粪尿途径排泄。OBJECTIVE To study the distribution,excretion and other pharmacokinetic characteristics of dual target ligand-based lidamycin(DTLL)in rats.METHODS[125 I]radioactivity isotope tracing method was used to determine the pharmacokinetic parameters of DTLL which was injected intravenously via the tail vein of healthy Wistar rats at a single dose of[125 I]DTLL 2625 k Bq·0.05 mg-1·kg-1.The samples from rat plasma,tissue,feces,urine and bile were obtained to analyze the distributions of DTLL in rats after administration and to calculate the cumulative excretion scores by using a liquid scintillation counting analyzer with the WinNolin program.RESULTS The area under the concentration-time curve(AUC0-∞)of DTLL was(184±33)h·μg·L-1,with half time(t1/2)and cleanrance(Cl)at(3.98±0.75)h and(278±41)mL·h-1·kg-1,respectively.DTLL was mainly distributed in whole body tissues without any accumulation observed.The excretion rate of DTLL was(82.5±2.6)%for urine,compared with(10.4±6.6)%in feces and(92.9±7.4)%in total.CONCLUSION DTLL is distributed rapidly in the whole body without obvious accumulation.Most of the DTLL administered is excreted through feces and urine.

关 键 词：双靶向配体化力达霉素 同位素 药动学 

分 类 号：R969.1[医药卫生—药理学]