聚乙二醇化蛋白質(zhì)（pegylated protein，PEG-蛋白質(zhì)）是延長蛋白質(zhì)類藥物半衰期的最有效的途徑之一，通過延緩蛋白的排泄，提高其抗酶解的能力，增加其溶解性與穩(wěn)定性，以及降低其免疫原性，可顯著延長蛋白質(zhì)類藥物體內(nèi)的生物活性，從而改善蛋白質(zhì)類藥物的藥代動力學和藥效學性質(zhì)。由于方法學上的限制，PEG-蛋白質(zhì)類藥物的代謝、組織分布和排泄研究極具挑戰(zhàn)，但眾多的文獻資料表明，聚乙二醇（polyethylene glycol，PEG）分子的體內(nèi)代謝與安全性已經(jīng)確立，無需過度擔心PEG-蛋白質(zhì)類藥物的安全性。將從PEG-蛋白質(zhì)體內(nèi)組織分布與排泄研究方法、PEG的代謝與安全性和PEG-蛋白質(zhì)類藥物動物和臨床應(yīng)用的安全性3方面介紹和評述PEG-蛋白藥物的體內(nèi)代謝與安全性評價問題。

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.