PEG修饰多肽HM-3大鼠体内组织分布和排泄  

Tissue Distribution and Excretion of PEGylation Polypeptide HM-3 in Rats

作　　者：刘振东[1] 常海民[1] 张奉国[1] 孙浩[1] 徐寒梅[1] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《药物生物技术》2011年第5期416-420,共5页Pharmaceutical Biotechnology

基　　金：国家"重大新药创制"科技重大专项(No.2009ZX09102)

摘　　要：研究PEG修饰抗肿瘤多肽HM-3单次尾静脉注射后在大鼠体内的组织分布特点和排泄途径,为临床试验提供依据。采用ELISA方法检测静脉注射修饰产物mPEG-SC_(20k)-HM-3后各时间点大鼠组织器官生物样品中药物的含量以及尿、粪和胆汁中mPEG-SC_(20k)-HM-3的排泄情况。大鼠单次静脉给予26mg/kg mPEG-SC_(20k)-HM-3后的组织分布试验表明,药物主要分布在大鼠肝和肾组织,其药物含量均于给药后1 h达最高,分别为(25.75±5.85)μg/g组织和(25.58±5.79)μg/g组织;大鼠静脉给予mPEG-SC_(20k)-HM-3(26 mg/kg)后从(0～104 h内)尿和粪中排泄的原型药物分别占给药总量的1.5%和0.02%;从(0～44 h内)大鼠胆汁中排泄的原型药物小于给药总量的0.1%。表明PEG修饰药物mPEG-SC_(20k)-HM-3主要分布在肝和肾组织,并主要由尿中排泄。To study characteristics of tissue distribution and excretion of PEG modified HM-3 after a single intravenous injection in rats and to provide the basis for clinical trials, the ELISA method was used to determine the drug concentration or the main metabolite excretion in biological samples and in urine,excrement and bile at different time points after intravenous injection of PEG modified HM-3 （mPEG-SC20k-HM-3）. The drug was mainly distributed in liver and kidney and achieved peak content after administration 1 h. The drug contents were （ 25.75± 5.85 ） μg/g tissue and （ 25.58 ± 5.79 ） μg/g in liver and kidney tissue respectively. The recovery of PEG modified HM-3 in urine and excrement excretion during 0 - 104 hours were 1.5% and 0.02% respectively,while the recovery during 0 - 44 hours was less than 0.1% in bile excretion. PEG modified HM-3 （ mPEG-SC20k-HM-3 ） has a tissue efficient distribution in liver and kidney and excretion mainly in urine.

关 键 词：PEG修饰 抗肿瘤多肽HM-3 SD大鼠 组织分布 排泄 

分 类 号：Q516[生物学—生物化学] R965[医药卫生—药理学]