基因重组人碱性成纤维细胞生长因子药物动力学实验研究──家兔静脉快推给药室分析

Experimental study on pharmacokinetics of genetic recombinativehuman basic fibroblast growth factor (rhbFGF)

目的：研究家兔静脉快推基因重组人碱性成纤维细胞生长因子（ｒｈｂＦＧＦ）后血药浓度随时间的变化关系，并对其代谢动力学参数进行估计。方法：家兔静脉一次快推ｒｈｂＦＧＦ４０００ＩＵ（１０μｇ），给药后１０，２０，３０ｍｉｎ及１．０，１．５，２．０，３．０，４．０，６．０，８．０ｈ耳缘静脉采血，放免分析法检测血中各个时间点的药物浓度。用数学方法拟合血药浓度－时间的函数关系，并估计药物动力学参数。结果：家兔静脉一次快推给药后血中ｒｈｂＦＧＦ浓度属双室模型一级动力学特征，其血药浓度－时间函数的解析表达式为：Ｃｔ＝９０．１１５６ｅ－２．０１０７ｔ＋１３．０７０７ｅ－０．１７８３ｔ。结论：本研究为指导ｒｈｂＦＧＦ的临床应用提供药物动力学的基本依据。

Objective:We observed the concentration changes of rhbFGF with time,and estimated the parameters of its pharmacokinetics in the blood of rabbit after a fast iv injection.Methods:The blood was collected from ear marginal veins 10,20 and 30 min and 1,1.5,2,3,4,6 and 8 h after a fast iv injection of rhbFGF 4000 IU(10 g).The blood concentrations of rhbFGF in different times were measured with radioimmunoassay.The functional relationship between blood rhbFGF concentration and time was fit with mathematical method,and the parameters of pharmacokinetics were estimated.Results:The rabbits blood concentrations of rhbFGF after a fast iv injection showed the characteristic of the first class kinetics of the model of two compartments.The analytic equation was Ct=90.1156e-2.0107t+13.0707e-0.1783t.Conclusion: The present study provides the experimental basis of pharmacokenitics for guiding clinical use of rhbFGF.