Pharmacokinetics of glycosylated recombinant human granulocyte colony-stimulating factor (lenograstim) in healthy male volunteers.
OBJECTIVE
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 microg 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 microg kg(-1) s.c. doses (mean peak=26.3x10(9) cells l(-1)), but on day 2 after 5 microg kg(-1) i.v. doses (mean peak = 12.4 x 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 microg 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.
Houston
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Quintiles (UK) Ltd, Bracknell.
Stevens
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LA
Cour
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D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000493:pharmacokinetics*; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001416:Back Pain / Q000139:chemically induced; D001682:Biological Availability; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D000078224:Lenograstim; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects; D010146:Pain / Q000139:chemically induced; D010612:Pharyngitis / Q000139:chemically induced; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D013997:Time Factors
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim