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

Abstract

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 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.

• Authors: A C Houston, L A Stevens, V Cour
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 47 Issue 3 Pg. 279-84 (Mar 1999) ISSN: 0306-5251 [Print] England
• PMID: 10215752 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Recombinant Proteins
• Granulocyte Colony-Stimulating Factor
• Lenograstim

Topics

• Adjuvants, Immunologic (adverse effects, pharmacokinetics)
• Adolescent
• Adult
• Area Under Curve
• Back Pain (chemically induced)
• Biological Availability
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Granulocyte Colony-Stimulating Factor (blood, pharmacokinetics, urine)
• Headache (chemically induced)
• Humans
• Infusions, Intravenous
• Injections, Subcutaneous
• Lenograstim
• Leukocyte Count (drug effects)
• Male
• Neutrophils (cytology, drug effects)
• Pain (chemically induced)
• Pharyngitis (chemically induced)
• Recombinant Proteins (blood, pharmacokinetics, urine)
• Time Factors