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目的研究聚乙二醇化重组人干扰素α-2b(PEG-rhIFNα-2b)的免疫原性及药物动力学性质,为药物评价提供数据支持。方法将rhIFNα-2b及PEG-rhIFNα-2b按照每日给药频率及临床给药频率腹腔免疫小鼠,分别采用ELISA间接法和细胞病变抑制法测定小鼠血清中结合抗体和中和抗体滴度;小鼠皮下单剂量注射rhIFNα-2b及PEG-rhIFNα-2b,采用ELISA双抗夹心法检测血清中的药物浓度,计算药物动力学参数。结果按每日给药频率时,rhIFNα-2b诱导产生的结合抗体和中和抗体滴度分别为7517.72和77.63,而PEG-rhIFNα-2b的分别为694.62和26.98;按临床给药频率时,rhIFNα-2b诱导产生的结合抗体和中和抗体滴度分别为5538.51和44.99,而PEG-rhIFNα-2b的分别为311.61和12.96;与rhIFNα-2b相比,PEG-rhIFNα-2b体内半衰期延长了约11倍。结论在该试验条件下,PEG修饰rhIFNα-2b可显著降低其免疫原性,延长体内半衰期。
Objective To study the immunogenicity and pharmacokinetics of pegylated recombinant human interferon α-2b (PEG-rhIFNα-2b) and provide data support for drug evaluation. Methods The mice were immunized intraperitoneally with rhIFNα-2b and PEG-rhIFNα-2b according to the frequency of daily administration and the frequency of clinical administration. ELISA titers and cytopathic effect ; Single subcutaneous injection of rhIFNα-2b and PEG-rhIFNα-2b, ELISA double-antibody sandwich method for the determination of serum drug concentration, calculate the pharmacokinetic parameters. Results According to the frequency of daily administration, the titers of binding antibody and neutralizing antibody induced by rhIFNα-2b were 7517.72 and 77.63, respectively, while those of PEG-rhIFNα-2b were 694.62 and 26.98, respectively. -2b induced 5538.51 and 44.99 titers of binding and neutralizing antibodies, respectively, compared to 311.61 and 12.96 for PEG-rhIFNα-2b, respectively; the in vivo half-life of PEG-rhIFNα-2b was prolonged by about 11 compared with rhIFNα-2b Times Conclusion Under these experimental conditions, PEG modified rhIFNα-2b can significantly reduce its immunogenicity and prolong the half-life in vivo.