PEG-EPO在大鼠体内的药代动力学研究

Study on pharmacokinetics of PEG-EPO in rats

目的:探讨聚乙二醇化促红细胞生成素(PEG-EPO)在大鼠体内的药代动力学。方法:采用放射性核素125I对PEG-EPO进行标记,测定高、中、低(27,9,3μg·kg-1)3个剂量组大鼠静脉注射125I-PEG-EPO后不同时间血浆中药物的放射性浓度,用DAS软件拟合放射性浓度-时间曲线,并计算药代动力学参数。结果:低、中、高3个剂量组给药后0.017h(1min)血药浓度分别为(24.800±3.535),(80.971±16.368),(269.620±26.360)ng·mL-1,与剂量呈正相关,r=0.9998;血中药物消除半衰期T1/2β分别为(27.22±3.67),(28.40±1.61),(33.12±1.83)h,随剂量的增加无显著变化;AUC0-120h分别为(69.22±7.13),(218.77±34.57),(470.42±65.88)ng·h·mL-1,与剂量呈正相关,r=0.9909。结论:PEG-EPO在大鼠体内的代谢过程呈线性动力学特征,符合二室开放模型。

Objective： To study the pharmacokinetics of PEG-EPO in rats. Methods： After labeled PEG-EPO by 125I, the radioactive drug concentrations in plasma were detected in different time points after that the rats were injected in high, middle or low doses （27, 9, 3 μg·kg^-1 ） of 125I-PEG-EPO. And then the concentration-time curves of 125I-PEG-EPO in plasma and pharmacokinetic parameters were got according to DAS program. Results： The plasma concentrations of 125I-PEG-EPO were （24.800 ± 3.535）, （80.971 ± 16：368）, （269.620 ±26.360） ng·mL^-1 respectively at 0.017 hour after the rats were injected in low, middle or high doses. There were positive correlation with doses （r = 0.999 8）. T1/2β of 125I-PEG-EPO were （27.22 ± 3.67）, （28.40 ± 1.61） and （33.12 ± 1.83） h respectively, which showed no significant changes although the doses increased. AUC0-120 h were （69.22 ± 7.13）, （218.77 ± 34.57）, （470.42 ± 65.88） ng-h·mL^-1 respectively, showing positive correlation with doses （r = 0.990 9）. Conclusion： The metabolism of PEG-EPO in rats shows the characters of linear kinetics, according with two compartment model.