ABSTRACT
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 microg (n = 8), 150 microg (n = 4), 300 microg (n = 4), 600 microg (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 Two subjects in the filgrastim 600-microg group were withdrawn for adverse events.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.
