title: Pegfilgrastim, a sustained-duration form of filgrastim, significantly improves neutrophil recovery after autologous marrow transplantation in rhesus macaques.
abstract: Daily administration of filgrastim decreases the duration of severe neutropenia in the clinical setting. A sustained-duration form of filgrastim, pegfilgrastim, significantly reduces scheduling protocols to a single injection per chemotherapy cycle while maintaining therapeutic efficiency. We examined the ability of a single injection of pegfilgrastim to significantly improve neutrophil recovery following autologous bone marrow transplantation (AuBMT) in rhesus macaques. On day 1, postmyeloablation (920 cGy x-irradiation) and AuBMT, animals received either 0.1% autologous serum for 18 consecutive days (n=13), or single doses of pegfilgrastim via the subcutaneous (s.c.) or intravenous (i.v.) route (300 or 100 micro g/kg), or a single dose of filgrastim at 300 micro g/kg via the s.c. or i.v. route, or filgrastim at 10 micro g/kg via the s.c. route (n=4) on a daily basis (range=days 12-17). Pharmacokinetic parameters and neutrophil recovery were assessed. A single dose of pegfilgrastim via the i.v. or s.c. route was as effective as daily filgrastim administration, resulting in significant improvement of neutrophil recovery after myeloablation and ABuMT. Effective pegfilgrastim plasma concentrations were maintained in neutropenic animals until after the onset of hematopoietic recovery. Enhanced pharmacokinetics in AuBMT cohorts are consistent with self-regulating, neutrophil-mediated clearance.
authors.affiliation: Greenebaum Cancer Center, University of Maryland, Baltimore, MD 21201, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Farese
authors.forename: B-B
authors.initials: BB
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Roskos
authors.forename: R B
authors.initials: RB
authors.lastname: Stead
authors.forename: T J
authors.initials: TJ
authors.lastname: MacVittie
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000379:methods*; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D009503:Neutropenia; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim