Pharmacology: Colony-stimulating factors are glycoproteins which act on hematopoietic cells by binding to specific cell surface receptors. Endogenous G-CSF is a lineage specific colony-stimulating factor which is produced by monocytes, fibroblasts, and endothelial cells. G-CSF regulates the production of neutrophils within the bone marrow and affects neutrophil progenitor proliferation, differentiation, and selected end-cell functional activation (including enhanced phagocytic ability, priming of the cellular metabolism associated with respiratory burst, antibody dependent killing, and the increased expression of some functions associated with cell surface antigens). G-CSF is not species specific and has been shown to have minimal direct in vivo or in vitro effects on the production of hematopoietic cell types other than the neutrophil lineage.
Pharmacokinetics: There is a positive linear correlation between the dose and the serum concentration of Filgrastim, whether administered intravenously or subcutaneously. Peak serum concentrations following subcutaneous injection are generally attained within 4-5 hours. The volume of distribution averaged 150 mL/kg. Clearance of Filgrastim has been shown to follow first-order pharmacokinetics after both subcutaneous and intravenous administration. The mean serum elimination half-life of Filgrastim is approximately 3.5 hours, with a clearance rate of approximately 0.6 mL/min/kg.
Toxicology: As with other therapeutic proteins, Filgrastim also has a potential for immunogenicity. However the incidence and effect of this has not been adequately determined. The carcinogenic and mutagenic potential of Filgrastim has not been studied. Single dose acute and chronic toxicity studies were conducted for Filgrastim (ReliGrast) with intramuscular and subcutaneous dosing in Swiss Albino mice (1000 mcg/kg body weight) and Sprague Dawley rats (500 mcg/kg body weight). The studies revealed no apparent toxicity in the test animals. Filgrastim (ReliGrast) did not cause any skin sensitization in test animals. It did not induce mutations in the mutagenicity model of Salmonella typhimurium.