【摘要】 目的研究聚乙二醇(PEG)修饰重组人干扰素-β(rhIFN-β)的免疫原性和药物代谢动力学性质。方法按照rhIFN-β的临床治疗程序免疫家兔,分别用ELISA方法和中和实验法检测家兔血清中的抗体水平;给家兔单剂量注射rhIFN-β及其3种修饰物,建立ELISA双抗体夹心法,检测血清中样品浓度。结果3种修饰物在家兔体内诱导产生的抗体水平均明显低于rhIFN-β诱导产生的抗体水平,半衰期分别较原来提高5.927倍、14.204倍和14.708倍。结论PEG修饰rhIFN-β可明显降低其免疫原性,改善了rhIFN-β的药物代谢动力学性质。更多还原

【Abstract】 Objective To study the immunogenicity and pharmacokinetics of PEG-rhIFN-β.Methods Immunize rabbits with three kinds of PEG-rhIFN-β every other day for 3 times,each at a dosage of 90 μg/kg body weight,and determine the serum antibody by ELISA and neutralization test.Inject rabbits with a single dose of the three kinds of PEG-rhIFN-β respectively and determine the concentrations of test samples in sera by double antibody sandwich ELISA.Results The antibody levels induced by the three kinds of PEG-rhIFN-β were significantly lower than that induced by rhIFN-β.However,compared with that of rhIFN-β,the half-life periods of the three kinds of PEG-rhIFN-β increased 5.927,14.204 and 14.708 folds respectively.Conclusion The modification with PEG decreased the immunogenicity of rhIFN-β significantly,but improved its pharmacokinetics.更多还原