Crossover study of the haematological effects and pharmacokinetics of glycosylated and non-glycosylated G-CSF in healthy volunteers.
A cross-over study of glycosylated and non-glycosylated G-CSF was performed in 20 healthy male volunteers to compare the effects of the different forms of G-CSF, the extent of inter-individual progenitor cell mobilization and to determine whether any differences observed were related to the serum concentrations of G-CSF attained. The peak WBC achieved during 6 d of G-CSF administration at a dose of 5 microg/kg/d was significantly higher with the glycosylated than the non-glycosylated product (P = 0.02) as was the peak level of granulocyte-monocyte colony forming cells (GM-CFC) (P=0.03). The average GM-CFC count on days 5, 6 and 7 was 28% higher with the glycosylated product (P=0.003). Serum concentrations of G-CSF achieved were significantly higher with the non-glycosylated G-CSF, however, suggesting that the difference in bio-efficacy was not due to a difference in G-CSF stability. Marked inter-individual variation in progenitor mobilization was observed, but this was not related to serum G-CSF levels. The G-CSF concentrations on day 6 were approximately one third of those on day 1, with both forms of G-CSF.
Watts
M J
MJ
University College London Medical School.
Addison
I
I
Long
S G
SG
Hartley
S
S
Warrington
S
S
Boyce
M
M
Linch
D C
DC
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D002455:Cell Division; D018592:Cross-Over Studies; D004311:Double-Blind Method; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D000078224:Lenograstim; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000166:cytology* / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018952:Antigens, CD34; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D000078224:Lenograstim; D000069585:Filgrastim