聚乙二醇修饰干扰素α2b的体内药代动力学研究

Study on the Pharmacokinetic of PEG-IFN α2b in vivo

目的 :运用同位素示踪法 -1 2 5I标记和 SDS-PAGE研究聚乙二醇修饰干扰素 α2 b的药代动力学。方法 :以大鼠为研究对象 ,分别按 1 ,3,5μg/ kg的剂量股静脉注射给药 ,颈动脉采血。利用 SDS-PAGE测定血液中原形药物放射量与总放射量的百分比 ,以校正全血血药浓度。用小鼠测定1 2 5I-干扰素 α2 b和 1 2 5I-单修饰干扰素α2 b的组织分布和尿粪排泄 ,用大鼠测定其胆汁排泄。结果 :1 2 5I-干扰 α2 b和 1 2 5I-单修饰干扰素 α2 b静脉注射给药符合一级消除动力学的二房室模型。按低 ,中 ,高三个剂量组 ,1 2 5I-干扰素α2 b的消除半衰期 ( t1 / 2 β)分别为 1 .0 2 0 ,0 .91 4 ,0 .6 6 5 h,1 2 5I-单修饰干扰素α2 b的消除半衰期 ( t1 / 2 β)分别为 2 .72 ,3.1 7,2 .6 9h,1 2 5I-单修饰干扰素α2 b在肾中的分布明显减少 ,在肝中的分布明显增加。结论 :聚乙二醇修饰能够显著延长干扰素 α2 b的体内半衰期。

AIM Tissue distribution and excretion of 125 I-mono-PEG-IFNα2b were studied using isotope tracing with 125 I-labellin and SDS-PAGE technique. METHODS The 125 I-labelled proteins were prepared by Iodogen method. The pharmacokinetic process was studied by iv injection of 1,3,5, μg/kg in rats. SDS-PAGE was utilized to determine the calibration coefficient, the proportion of protein band radioactivity to total radioactivity in blood, to modify the blood concentration. RESULTS The concentration-time curves of the two proteins were fitted to two-compartment model, and AUCs were linearly related to the dosages. The t-{1/2β} values of 125 I-IFN α2b were 1.02 h, 0.914 h and 0.665 h, while 125 I-mono-PEG-IFNα2b were 2.72 h, 3.12 h and 2.69 h. Distribution of 125 I-mono-PEG-IFNα2b in kidney was notably decreased in comparison with 125 I-IFNα2b, however, 125 I-mono-PEG-IFNα2b was evidently increased in liver. CONCLUSION The half life of IFN α2b was apparently increased because of PEG modification.=