摘要
聚乙二醇化蛋白质(pegylated protein,PEG-蛋白质)是延长蛋白质类药物半衰期的最有效的途径之一,通过延缓蛋白的排泄,提高其抗酶解的能力,增加其溶解性与稳定性,以及降低其免疫原性,可显著延长蛋白质类药物体内的生物活性,从而改善蛋白质类药物的药代动力学和药效学性质。由于方法学上的限制,PEG-蛋白质类药物的代谢、组织分布和排泄研究极具挑战,但众多的文献资料表明,聚乙二醇(polyethyleneglycol,PEG)分子的体内代谢与安全性已经确立,无需过度担心PEG-蛋白质类药物的安全性。将从PEG-蛋白质体内组织分布与排泄研究方法、PEG的代谢与安全性和PEG-蛋白质类药物动物和临床应用的安全性3方面介绍和评述PEG-蛋白药物的体内代谢与安全性评价问题。
Pegylation is one of the most effective methods to prolong the serum half-life of therapeutic protein drugs, by delaying clearance, increasing solubility as well as stability, protecting against susceptibility to enzymatic degradation, and reducing immunogenicity. The PEGylated proteins have also enhanced their pharmacokinetic and pharmacodynamic performance along with sustained actions. However, it is a significant challenge for studying the metabolism, distribution and excretion of PEGylated proteins because of the limitation of methods. Fortunately, literature data indicate that the polyethylene glycol （PEG） associated with a protein should provide no extra concern because the exposure-toxicity relationship of PEG between animals and humans has been thoroughly investigated and metabolism / excretion of PEG is well understood. We reviewed the metabolism and safety evaluation of PEGylated proteins, through introduction and assessment of the method limited for studying distribution and excretion, the in vivo metabolism and safety of PEG, and the toxicity of PEGylated proteins in animals and humans.
出处
《药物评价研究》
CAS
2010年第4期249-253,共5页
Drug Evaluation Research
