Baumann Andreas, Tuerck Dietrich, Prabhu Saileta, Dickmann Leslie, Sims Jennifer
Bayer Pharma AG, Berlin, Germany.
F. Hoffmann-La Roche AG, Basel, Switzerland.
Drug Discov Today. 2014 Oct;19(10):1623-31. doi: 10.1016/j.drudis.2014.06.002. Epub 2014 Jun 11.
The pharmacokinetics (PK), metabolism and biodistribution of polyethylene glycol (PEG) in PEGylated proteins are important to understand the increased cellular vacuolation reported in various tissues in animals. The tissue distribution profile of PEGylated proteins and 'metabolic' PEG is guided largely by absolute PEG load, PEG molecular weight and, where applicable, receptor-mediated uptake via the protein moiety. High molecular weight PEGs show slow renal clearance, and consequently have a greater potential to accumulate within cells. The intracellular nonbiodegradable PEG can accumulate within the lysosome ultimately causing distension and vacuolation observed by standard histological examinations. Improved bioanalytical methodologies will contribute to the identification of specific PK parameters including distribution behavior to support development of PEGylated proteins as therapeutics.
聚乙二醇化蛋白质中聚乙二醇（PEG）的药代动力学（PK）、代谢和生物分布对于理解动物各种组织中报道的细胞空泡化增加很重要。聚乙二醇化蛋白质和“代谢性”PEG的组织分布概况在很大程度上由绝对PEG负载量、PEG分子量以及（如适用）通过蛋白质部分的受体介导摄取所引导。高分子量PEG显示出缓慢的肾脏清除率，因此在细胞内积累的潜力更大。细胞内不可生物降解的PEG可在溶酶体内积累，最终导致标准组织学检查中观察到的扩张和空泡化。改进的生物分析方法将有助于确定特定的PK参数，包括分布行为，以支持聚乙二醇化蛋白质作为治疗药物的开发。
