Pharmacokinetics, metabolism and distribution of PEGs and PEGylated proteins: quo vadis?

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / pharmacokinetics*
  • Proteins / chemistry
  • Proteins / pharmacokinetics*
  • Tissue Distribution


  • Proteins
  • Polyethylene Glycols