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PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals

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PEGylated Protein Drugs: Basic Science and Clinical Applications

Part of the book series: Milestones in Drug Therapy ((MDT))

Abstract

PEG is used to improve pharmacokinetic properties of biologicals. Concern has been expressed about the toxicological effect and/or fate of the PEG. This paper reviews the available toxicity, metabolism and clearance data of PEG and PEGylated products in order to place such concerns in to appropriate context. The available data demonstrates that PEG itself only shows toxicity at high, parenteral doses and the usual target organ is the kidney as this is the route of excretion for unchanged PEG. A large therapeutic window (approximately 600-fold) exists between the maximum PEG burden from a current biological agent and the doses of PEG associated with human toxicity. Pathological changes which results in no functional deficit, PEG containing vacuoles in cells, have been observed with PEGylated biologicals. There is evidence that these PEG vesicle can resolve with time. In conclusion the doses used clinically for current and many future PEGylated biologicals are low and will result in exposures to PEG significantly lower than that required to elicit PEG toxicity. In all cases the routine regulatory toxicology studies would identify relevant pathology should it occur.

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Author information

Authors and Affiliations

  1. Pharmacokinetics, Dynamics and Metabolism, Pfizer Global Research and Development, Kent, CT13 9NJ, UK

    Rob Webster & Donald Walker

  2. MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, L69 3BX, UK

    Victoria Elliott & B. Kevin Park

  3. DSRD, Pfizer Global Research and Development, Kent, CT139NJ, UK

    Mark Hankin & Philip Taupin

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  1. Rob Webster
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  2. Victoria Elliott
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  3. B. Kevin Park
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  4. Donald Walker
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  5. Mark Hankin
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  6. Philip Taupin
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Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Sciences, University of Padova, 35131, Padova, Italy

    Francesco M. Veronese

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© 2009 Birkhäuser Verlag/Switzerland

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Webster, R., Elliott, V., Park, B.K., Walker, D., Hankin, M., Taupin, P. (2009). PEG and PEG conjugates toxicity: towards an understanding of the toxicity of PEG and its relevance to PEGylated biologicals. In: Veronese, F.M. (eds) PEGylated Protein Drugs: Basic Science and Clinical Applications. Milestones in Drug Therapy. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8679-5_8

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