Granulocyte colony-stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor.
BACKGROUND
Recombinant granulocyte colony-stimulating factor (rG-CSF) has been suggested as a treatment for certain varieties of neonatal neutropenia, but little is known about the pharmacologic disposition of rG-CSF in that population.


METHODS
Ten neutropenic neonates were treated with rG-CSF, 10 micrograms/kg intravenously once daily for 3 to 5 days. Serum and urine samples were obtained before rG-CSF dosing and at intervals thereafter for G-CSF quantification by enzyme-linked immunosorbent assay.


RESULTS
Five of the neutropenic neonates (termed group 1) were not infected but likely had hyporegenerative neutropenia (4 were born after pregnancy-induced hypertension/intrauterine growth restriction, and 1 had Rh hemolytic disease). Five other infants (group 2) had neutropenia accompanying bacterial sepsis and shock. Before receiving the first dose of rG-CSF, endogenous G-CSF serum and urine concentrations were relatively low in group 1, averaging 130 pg/mL (range: 48-209) in serum and 53 pg/mL (range: 15-141) in urine. Serum concentrations immediately before the final dose were much higher (range: 81-24 835 pg/mL), whereas urine concentrations were unchanged (range: <7 pg/mL-126 pg/mL). In group 2 patients, before receiving the first-dose of rG-CSF, endogenous concentrations were very high, averaging 59 575 pg/mL (range: 20 028-98 280) in serum and 3189 pg/mL (range: 23-4770) in urine. Predose serum concentrations before the final dose (range: 427-14 460 pg/mL) were lower than before the first dose. The area under the concentration curve after the first dose of rG-CSF administration in group 1 was significantly lower than after the first dose in group 2, but no difference in area under the concentration curve was observed between groups 1 and 2 after the last dose of rG-CSF.


CONCLUSIONS
The principal means of clearing G-CSF from the serum is by saturable binding to specific G-CSF receptors (G-CSF-Rs). Therefore, the very high G-CSF serum and urine concentrations of group 2 patients before the first rG-CSF dose implies that their G-CSF-Rs were saturated before the dose was given. We speculate that if G-CSF-Rs are saturated with endogenous G-CSF, treatment with rG-CSF will add little or nothing to the granulocytopoietic effort. On this basis, we judge that neonates with septic shock and neutropenia are unlikely to derive benefit from rG-CSF administration.
Calhoun
D A
DA
Department of Pediatrics, Division of Neonatology, and the Clinical Research Center, University of Florida College of Medicine, Gainesville 32610-0296, USA. calhoda@peds.ufl.edu
Lunøe
M
M
Du
Y
Y
Hutson
A D
AD
Veerman
M
M
Christensen
R D
RD
D004797:Enzyme-Linked Immunosorbent Assay; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000097:blood* / Q000652:urine*; D006801:Humans; D007231:Infant, Newborn; D007275:Injections, Intravenous; D007958:Leukocyte Count; D009503:Neutropenia / Q000097:blood / Q000209:etiology / Q000628:therapy* / Q000652:urine; D009504:Neutrophils; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor