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Development of Pegylated Interferons for the Treatment of Chronic Hepatitis C

Kozlowski A ; Charles S.A ; Harris J.M

BioDrugs, 2001-07-01, Vol.15 (7), p.419-429 [Peer Reviewed Journal]

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  • Title:
    Development of Pegylated Interferons for the Treatment of Chronic Hepatitis C
  • Author: Kozlowski A ; Charles S.A ; Harris J.M
  • Subjects: Hepatitis C, treatment ; PEG interferon alpha 2a, therapeutic use ; PEG interferon alpha 2b, therapeutic use ; Antivirals, therapeutic use ; Research and development ; Antibodies ; Pharmacotherapy ; Cancer Research ; Molecular Medicine ; Biomedicine ; Antiviral Agents - therapeutic use ; Humans ; Interferon-alpha - pharmacokinetics ; Interferon-alpha - therapeutic use ; Polyethylene Glycols - pharmacokinetics ; Recombinant Proteins ; Hepatitis C, Chronic - drug therapy ; Polyethylene Glycols - therapeutic use
  • Is Part Of: BioDrugs, 2001-07-01, Vol.15 (7), p.419-429
  • Description: The chemical attachment of poly(ethylene glycol) [PEG] to therapeutic proteins produces several benefits, including enhanced plasma half-life, lower toxicity, and increased drug stability and solubility. In certain instances, pegylation of a protein can increase its therapeutic efficacy by reducing the ability of the immune system to detect and mount an attack on the compound.A PEG-protein conjugate is formed by first activating the PEG moiety so that it will react with, and couple to, the protein. PEG moieties vary considerably in molecular weight and conformation, with the early moieties (monofunctional PEGs; mPEGs) being linear with molecular weights of 12kD or less, and later moieties being of increased molecular weights. PEG2, a recent innovation in PEG technology, involves the coupling of a 30kD (or less) mPEG to lysine that is further reacted to form a branched structure that behaves like a linear mPEG of much larger molecular weight. These compounds are pH and temperature stable, and this factor along with the large molecular weight may account for the restricted volume of distribution seen with drugs utilising these reagents.Three PEG-protein conjugates are currently approved for clinical use in the US, with more under clinical development. Pegademase is used in the treatment of severe combined immunodeficiency disease, pegaspargase for the treatment of various leukaemias, and pegylated interferon- for chronic hepatitis C virus infections. As illustrated in the case of the 2 pegylated interferon-s, all pegylated proteins are not equal. The choice of PEG reagent and coupling chemistry is critical to the properties of the PEG-protein conjugate, with the molecular weight of the moiety affecting its rate and route of clearance from the body, and coupling chemistry affecting the strength of the covalent attachment of PEG to therapeutic protein.
  • Publisher: Cham: Adis International
  • Language: English
  • Identifier: ISSN: 1173-8804
    EISSN: 1179-190X
    DOI: 10.2165/00063030-200115070-00001
    PMID: 11520253

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