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Pegfilgrastim — designing an improved form of rmetHuG-CSF

  • Graham Molineux
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

rmetHuG-CSF is the recombinant version of natural granulocyte colony-stimulating factor, the dominant stimulator in the production of neutrophilic leukocytes (neutrophils). Neutrophils represent the first line of defense against invading pathogens and when neutrophil numbers are suppressed by cancer chemotherapy, patients become liable to life-threatening infections.

The clearance of rmetHuG-CSF is effected by a combination of neutrophil mediated degradation and renal filtration. Site-directed addition of a single, linear PEG molecule yielded a form of G-CSF (pegfilgrastim) that was shown to be resistant to renal elimination yet remained sensitive to neutrophilmediated destruction. This semi-synthetic cytokine drug can persist in the plasma for extended periods in neutropenic conditions, yet is cleared rapidly when neutrophils recover. This lends a degree of automation to the therapeutic control of neutrophil numbers which has been exploited in clinical practice since its approval for human use in 2002.

Keywords

Granulocyte Colony Stimulate Factor Darbepoetin Alfa Peripheral Blood Progenitor Cell Severe Congenital Neutropenia Experimental Hematology 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Graham Molineux
    • 1
  1. 1.Amgen Inc.One Amgen Center DriveThousand OaksUSA

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