摘要
目的探究粒细胞集落刺激因子(G-CSF)的Fc融合蛋白Fc-G-CSF在大鼠体内的药代动力学、组织分布和排泄特点。方法采用氯胺T方法对Fc-G-CSF进行^125I标记,并应用三氯醋酸(TCA)沉淀方法测定各生物样本中的^125I-Fc-G-CSF的含量。结果大鼠单次皮下注射^125I-Fc-G-CSF 30μg/kg后,药时曲线下面积AUC为(362.1±48.1)μg·h/L,Cmax为(27.0±3.0)μg/L;给药后36 h,药物暴露量血清最高,脑组织最低;给药后96 h,经尿累积排泄率约为57.5%,经粪便累计排泄率约为23.5%。结论大鼠皮下注射^125I-Fc-G-CSF 12 h后血药浓度达峰,血清中浓度持续高于其他组织,排泄主要通过尿液进行。
Objective To investigate the pharmacokinetics,tissue distribution and excretion characteristics of Fc-G-CSF(the fusion protein of Fc and granulocyte colony stimulating factor)in rats.Methods Fc-G-CSF was labeled with ^125I by the chloramine T method,and the content of ^125I-Fc-G-CSF in each biological sample was determined by the trichloroacetic acid(TCA)precipitation method.Results After a single subcutaneous injection of ^125I-Fc-G-CSF 30μg/kg,the AUC was(362.1±48.1)μg·h/L and the Cmax was(27.0±3.0)μg/L.Up to 36 hours of the drug administration,the drug exposure was highest in serum but lowest in brain.Up to 96 hours of the drug administration,the cumulative excretion rate through urine was about 57.5%,and the cumulative excretion rate through feces was about 23.5%.Conclusion The blood concentration of ^125I-Fc-G-CSF reached a peak after 12 h of the subcutaneous injection in rats,and the serum concentration was continuously higher than the concentrations in other tissues.The ^125I-Fc-G-CSF excretion mainly adopted the urinary excretion.
作者
孙云波
韩鹏
刘桃云
窦桂芳
SUN Yun-bo;HAN Peng;LIU Tao-yun;DOU Gui-fang(Institute of Radiation Medicine,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)
出处
《国际药学研究杂志》
CAS
北大核心
2020年第4期296-299,共4页
Journal of International Pharmaceutical Research
关键词
粒细胞集落刺激因子
药代动力学
生物分布
排泄
granulocyte colony stimulating factor(GCSF)
pharmacokinetics
tissue distribution
excretion