title: Pharmacokinetics, metabolism and distribution of PEGs and PEGylated proteins: quo vadis?
abstract: 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.
authors.affiliation: Bayer Pharma AG, Berlin, Germany. Electronic address: andreas.baumann@bayer.com.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baumann
authors.affiliation: F. Hoffmann-La Roche AG, Basel, Switzerland.
authors.forename: Dietrich
authors.initials: D
authors.lastname: Tuerck
authors.affiliation: Genentech, South San Francisco, USA.
authors.forename: Saileta
authors.initials: S
authors.lastname: Prabhu
authors.affiliation: Genentech, South San Francisco, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Dickmann
authors.affiliation: Integrated Biologix, Basel, Switzerland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sims
mesh_terms: D000818:Animals; D006801:Humans; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics*; D011506:Proteins / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D011506:Proteins; D011092:Polyethylene Glycols