Pharmacokinetics of pegfilgrastim.
Pegfilgrastim is a granulocyte colony-stimulating factor (G-CSF) with a long half-life and sustained duration of action. Pegfilgrastim is created with pegylation technology, whereby a 20-kD polyethylene glycol moiety is conjugated to filgrastim (recombinant human G-CSF), resulting in a larger molecule. Consequently, its renal clearance by glomerular filtration is minimized, making neutrophil-mediated clearance the predominant route of elimination. Preclinical animal data have shown that the clearance of pegfilgrastim depends on dosage and absolute neutrophil count, with pegfilgrastim having a longer circulating half-life and more sustained duration of action than filgrastim. The biologic effect of pegfilgrastim is prolonged in a neutropenic setting because few mature neutrophils are available to mediate its elimination. Clinical trials have suggested that neutrophil-mediated clearance of pegfilgrastim may be self-regulating and may therefore be specific to each patient's hematopoietic recovery.
Zamboni
William C
WC
Program of Molecular Therapeutics and Drug Discovery, University of Pittsburgh Cancer Institute, UPCI Research Pavilion, The Hillman Cancer Center, 5117 Centre Avenue, G.27C, Pittsburgh, PA 15213-1863, USA. zamboniwc@msx.upmc.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D019540:Area Under Curve; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D008657:Metabolic Clearance Rate; D009503:Neutropenia / Q000139:chemically induced / Q000188:drug therapy; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim