Pegfilgrastim Neulasta

The attachment of polyethylene glycol (PEG) to proteins (pegylation) is a well-tested method of modifying their characteristics without substantially affecting their primary target (34-40). The tactic has been used to extend serum residence time, reduce immunogenicity, protect from proteolytic degradation, and improve formulation characteristics (41). Not surprisingly, pegylation of G-CSF has been reported several times (42-46). The first, and to date only, pegylated G-CSF to be made available for clinical use is a derivative of filgrastim, pegfilgrastim, which was approved for human use in the United States, Canada, Australia, and Europe in 2002 (47-51). The molecular nature of the derivation is a 20-kDa, linear PEG that is covalently attached to the N-terminus of filgrastim (36). This material retains its ability to stimulate neutrophil production over a longer period because of its altered residence time in the circulation (52). It also displays some unique pharmacokinetic properties that are more fully explained below (see Subheading 3.2.), but in effect presents a "self-regulating" form of rHuG-CSF ideal for use in chemotherapy-induced neutropenia.

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