title: Pharmacokinetic/pharmacodynamic modeling of pegfilgrastim in healthy subjects.
abstract: This analysis was conducted to characterize the pharmacokinetics and pharmacodynamics of pegfilgrastim and to develop a pharmacokinetic-pharmacodynamic model to describe the granulopoietic effects of pegfilgrastim and the homeostatic regulation of pegfilgrastim clearance in healthy subjects. Pegfilgrastim serum concentration data and differential white cell counts were obtained from an open-label, single-dose, dose escalation study. Healthy subjects (8 subjects/dose group) received a single subcutaneous dose of 30, 60, 100, or 300 microg/kg pegfilgrastim. Pegfilgrastim exhibited nonlinear pharmacokinetics; clearance decreased with increasing dose. A dose-dependent increase in absolute neutrophil count with an increase in the percentage of band cells was observed. A pharmacokinetic-pharmacodynamic model was developed that adequately described the nonlinear pharmacokinetics of pegfilgrastim, feedback regulation of pegfilgrastim clearance by neutrophils, and the differential effects of pegfilgrastim on neutrophil populations in blood.
authors.affiliation: Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320, USA.
authors.forename: Lorin K
authors.initials: LK
authors.lastname: Roskos
authors.forename: Peggy
authors.initials: P
authors.lastname: Lum
authors.forename: Pamela
authors.initials: P
authors.lastname: Lockbaum
authors.forename: Gisela
authors.initials: G
authors.lastname: Schwab
authors.forename: Bing-Bing
authors.initials: BB
authors.lastname: Yang
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D007279:Injections, Subcutaneous; D007958:Leukocyte Count; D008954:Models, Biological; D009504:Neutrophils / Q000187:drug effects*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012016:Reference Values
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim