Effect of escalating doses of recombinant human granulocyte colony—stimulating factor (filgrastim) on circulating neutrophils in healthy subjects

• Published in: Clinical Therapeutics Vol. 20; no. 4; pp. 722 - 736
• Main Authors: Borleffs, Jan C.C., Bosschaert, Mike, Vrehen, Henk M., Schneider, Margriet M.E., van Strijp, Jos, Small, Maria K., Borkett, Keith M.
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01.07.1998; Elsevier BV; Excerpta Medica
• Subjects: Adult; Biological and medical sciences; Blood. Blood coagulation. Reticuloendothelial system; Dose-Response Relationship, Drug; Double-Blind Method; Filgrastim; Granulocyte Colony-Stimulating Factor; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - blood; Granulocyte Colony-Stimulating Factor - pharmacokinetics; Humans; Leukocyte Count; Leukocyte Count - drug effects; Male; Medical sciences; neutrophil function; Neutrophils; Neutrophils - cytology; Neutrophils - drug effects; normal volunteers; pharmacokinetics; Pharmacology. Drug treatments; Placebos; Recombinant Proteins; filgrastim; pharmacokinetics; normal volunteers; neutrophil function; granulocyte colony—stimulating factor; Multiple dose; Human; Granulocyte colony stimulating factor; Toxicity; Subcutaneous administration; Neutrophil; Recombinant protein; Normal; Pharmacokinetics; Filgrastim; Dose activity relation
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(98)80135-5

The safety profile, tolerability, pharmacodynamics, and pharmacokinetics of four doses of recombinant human granulocyte colony—stimulating factor (filgrastim) were assessed in healthy volunteers in a double-masked, placebo-controlled, parallel-group trial. Healthy subjects received subcutaneous injections of filgrastim 75 μg (n = 8), 150 μg (n = 4), 300 μg (n = 4), 600 μg (n = 8), or placebo (n = 6) daily for 10 consecutive days. Blood samples were drawn daily immediately before the injection and on days 1 and 10 serially throughout the day. Increased absolute neutrophil counts (ANCs) were seen within 90 minutes of drug administration in subjects in all dose groups, peaking approximately 12 hours after administration. This increase was dose related in subjects in the three lower dose groups. The time to peak ANC on day 10 was approximately 9 hours, with a daily ANC profile in all four dose groups that was similar to the profile on day 1. In all dose groups, ANCs were near baseline within 48 hours of discontinuation of filgrastim. Mild, reversible thrombocytopenia was reported in 4 of 10 subjects in the highest dose group. Two subjects in the filgrastim 600-μg group were withdrawn for adverse events. Filgrastim had a good safety profile and caused dose-related increases in ANC when administered to healthy volunteers for up to 10 days.