The covalent conjugation of polyethylene glycol (PEG, typical MW>10k) to therapeutic proteins is a well-established and attractive technology that significantly increases biologic t1/2 and diminishes the potential for immunogenicity of the therapeutic proteins. PEG is generally considered inert and safe in animals and humans. However, the tissue distribution, the extent of accumulation in tissues after multiple doses, and the clearance of PEG-related components have not been adequately characterized. Moreover, the slow clearance of large PEGs in humans and animals raises the concerns about potential adverse effects resulting from PEG accumulation in tissues with chronic administration. In an effort to better understand PEG disposition following dosing with PEGylated proteins, we have established methodologies utilizing either sensitive LC/MS method or radioactivity detection for the quantitative analysis of PEG in tissues and blood. The development of these methodologies and preliminary data on PEG disposition in animals dosed with either a tool PEGylated protein or PEG alone will be presented.

Tissue distribution of PEG and PEGylated proteins following intravenous doses to animals

248th National Meeting (2014)

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