G-CSF serum pharmacokinetics during peripheral blood progenitor cell mobilization: neutrophil count-adjusted dosage might potentially improve mobilization and be more cost-effective.
The optimal dosing schedule of G-CSF for peripheral blood progenitor cell (PBPC) mobilization is still under investigation although many centers use 10 microg/kg/day in a single subcutaneous dose. However, G-CSF clearance increases with increasing absolute neutrophil count (ANC). Hence a G-CSF dosage adjusted to ANC might be a reasonable approach. We measured G-CSF trough serum levels by sandwich ELISA assay at different ANCs in eight patients undergoing treatment with filgrastim at 10 microg/kg/day in a single subcutaneous dose. A total of 26 samples were analyzed, and a strong correlation between increasing ANC and decreasing G-CSF levels was found by linear regression analysis (P < 0.0003, r2 = 0.4199). For ANC values above 5000/microl the trough serum levels, ie 24 h after administration, were consistently below the level that provides maximal clonogenic precursor stimulation in vitro (10 ng/ml). Serial serum G-CSF measurements performed in three patients at 0, 3, 6, 9 and 24 h after G-CSF administration, showed a reduction of the area under the curve (AUC) with increasing ANC. For an ANC of 20000/microl or greater, the G-CSF serum level fell under the maximal in vitro stimulation threshold of 10 ng/ml within 12 h. This preliminary pharmacokinetic data seems to suggest that an ANC-adjusted G-CSF dosing schedule might improve the design of PBPC mobilization regimens.
Faulkner
L B
LB
Department of Pediatrics, University of Florence, Ospedale Pediatrico A Meyer, Italy.
Tucci
F
F
Tamburini
A
A
Tintori
V
V
Lippi
A A
AA
Bambi
F
F
Malentacca
F
F
Azzari
C
C
Gelli
A M
AM
Genovese
F
F
Bernini
G
G
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003362:Cost-Benefit Analysis; D004334:Drug Administration Schedule; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000097:blood* / Q000191:economics; D019650:Hematopoietic Stem Cell Mobilization / Q000191:economics / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D007958:Leukocyte Count; D009369:Neoplasms / Q000628:therapy; D009504:Neutrophils
D016179:Granulocyte Colony-Stimulating Factor