Pharmacokinetics of glycosylated recombinant human granulocyte colony‐stimulating factor (lenograstim) in healthy male volunteers

Aims  The aim of this open, randomised, crossover, parallel‐group study was to compare the pharmacokinetics and neutrophil responses of lenograstim when administered subcutaneously (s.c.) and intravenously (i.v.).Methods A total of 27 healthy male volunteers was recruited. Lenograstim doses (0.5, 2, 5, or 10 μg kg −1  ) were administered s.c. or i.v. once‐daily for 5 days, and then, after a 10‐day washout period, vice versa for a further 5 days. Lenograstim concentrations and absolute neutrophil counts (ANCs) were measured predosing and postdosing on days 1 and 5.Results Maximum serum concentrations of lenograstim were higher following i.v. dosing (mean 5.2–185.5 vs 0.7–30.0 ng ml −1 after s.c. dosing on day 1) and attained sooner (median 0.5–0.8 vs 4.7–8.7 h on day 1). However, apparent elimination half‐lives of lenograstim were longer following s.c. dosing (mean 2.3–3.3 vs 0.8–1.2 h after i.v. dosing on days 1 and 5). ANCs increased in a dose‐dependent manner with both routes of lenograstim, but more prolonged rises and higher ANC peaks were attained following s.c. doses. ANCs peaked on day 6 following 5 μg kg −1 s.c. doses (mean peak=26.3×10 9 cells l −1  ), but on day 2 after 5 μg kg −1 i.v. doses (mean peak=12.4×10 9 cells l −1  ). Irrespective of route, the most common adverse events were headaches and back/spine pain; at doses of up to 5 μg kg −1 these were mild and generally well tolerated.Conclusions  While supporting the use of both s.c. and i.v. administered lenograstim to treat neutropenia, these results demonstrate that neutrophil responses are more sustained and prolonged with the s.c. route.