title: Prevention of chemotherapy-induced neutropenia with pegfilgrastim: pharmacokinetics and patient outcomes.
abstract: Patients receiving cytotoxic chemotherapy are at risk for developing chemotherapy-induced neutropenia (CIN). Filgrastim, a recombinant granulocyte colony-stimulating factor (G-CSF) that stimulates the proliferation, differentiation and function of neutrophils, is approved for the prevention of CIN. To eliminate the burden of daily filgrastim injection, pegfilgrastim, a long-acting form of filgrastim, was developed by covalently attaching a 20-kDa polyethylene glycol molecule to filgrastim to increase molecular size and thus reduce renal elimination. Consequently, neutrophil-mediated clearance is the primary mechanism for pegfilgrastim elimination. Therefore, after a single pegfilgrastim injection following chemotherapy treatment, pegfilgrastim concentration is sustained during neutropenia and decreases with neutrophil recovery. Pegfilgrastim has received marketing authorization approval from many regions to reduce the incidence of CIN based on the similar efficacy and safety of a single injection of 6 mg of pegfilgrastim administered once per chemotherapy cycle and 10 to 11 daily injections of filgrastim at 5 µg/kg. The efficient self-regulating clearance of pegfilgrastim allows administration once per chemotherapy cycle, thereby providing a more convenient treatment regimen than filgrastim.
authors.affiliation: Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., Thousand Oaks, CA 91320, USA. byang@amgen.com
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Yang
authors.forename: Michael A
authors.initials: MA
authors.lastname: Savin
authors.forename: Michael
authors.initials: M
authors.lastname: Green
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim