聚乙二醇修饰对重组人促红细胞生成素在大鼠体内药代动力学的影响

Effect of PEG-modification on the pharmacokinetics of recombinant human erythropoietin in rats

目的:研究聚乙二醇修饰对重组人促红细胞生成素在大鼠体内药代动力学的影响。方法:大鼠随机分成3组,分别单次皮下注射5μg·kg-1氨基葡萄糖-聚乙二醇-EPO(G-PEG-EPO)、甲氧基-聚乙二醇-EPO(M-PEG-EPO)和未经修饰的EPO原液后采集血样,采用酶联免疫吸附分析(ELISA)测定大鼠血浆样品中的EPO浓度。结果:给药后,与EPO相比,M-PEG-EPO,G-PEG-EPO较EPO吸收过程缓慢,峰浓度Cmax水平显著降低,代谢清除相对缓慢,末端消除相半衰期t1/2明显延长。而M-PEG-EPO,G-PEG-EPO的药代动力学参数除AUC0～inf和Cls外均无统计学差异。结论:聚乙二醇修饰能显著延长EPO在大鼠的末端消除相半衰期,G-PEG-EPO和M-PEG-EPO在大鼠的药代动力学性质相似。

Objective： To determine the effect of PEG-modification on the pharmacokinetics of recombinant human erythropoietin in rats. Methods： Eighteen rats were equally randomized into three groups. EPO, M-PEG- EPO and G-PEG-EPO at 5μg·kg^-1 were subcutaneously injected, respectively. Enzyme-linked immunosorbent as- say （ELISA） was used to investigate the plasma concentrations of EPO, M-PEG-EPO and G-PEG-EPO. Results： After administration, the Tmax of M-PEG-EPO and G-PEG-EPO was later than that of EPO. The peak concentrations of M-PEG-EPO and G-PEG-EPO in plasma were lower than that of EPO. M-PEG-EPO and G-PEG-EPO were cleared slower as the terminal half-life was prolonged relatively. There was no statistically significant difference be- tween M-PEG-EPO and G-PEG-EPO in pharmacokinetics parameters except AUC0_i.f and Cl. Conclusion： PEG- modification of EPO can prolong the terminal half-life of EPO in rats. The pharmacokineties of M-PEG-EPO and G- PEG-EPO in rats is similar.