^125I-Fc-G-CSF 在大鼠体内的药代动力学及组织分布

Pharmacokinetics and tissue distribution of ^125I-Fc-G-CSF in rats

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.