摘要
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 polyethylene glycol recombinant human Interferon α-2b(PEG-rhIFNα-2b) in mouse.Methods Immunizing mouse with rhIFNα-2b and PEG-rhIFNα-2b according to daily and clinical administration by ip administration,then determine the serum combining and neutralizing antibody by ELISA and cytopathogenic effect inhibition assay.Injecting mouse with a single dose of rhIFNα-2b and PEG-rhIFNα-2b respectively and determining the concentrations of samples in sera by ELISA and analyze the pharmacokinetic parameter.Results The combining antibody titer and the neutralizing antibody titer are 7517.72 and 77.63 induced by rhIFNα-2b,while the titers are 694.62 and 26.98 induced by PEG-rhIFNα-2b according to daily administration.The two types of antibody titers are 5538.51 and 44.99 induced by rhIFNα-2b,while those are 311.61 and 12.96 induced by PEG-rhIFNα-2b according to clinical administration.The half-life of rhIFNα-2b was increased almost 11-fold by pegylation.Conclusion The rhIFNα-2b modified with PEG significantly decreased the Immunogenicity and prolonged the half-life.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2010年第4期282-284,共3页
Journal of Toxicology
基金
安徽省科技攻关计划(09010301018)
关键词
聚乙二醇
干扰素Α-2B
免疫原性
药物动力学
polyethylene glycol
recombinant human Interferon α-2b
immunogenicity
pharmacokinetics