RT Journal Article
SR Electronic
T1 Granulocyte Colony-Stimulating Factor Serum and Urine Concentrations in Neutropenic Neonates Before and After Intravenous Administration of Recombinant Granulocyte Colony-Stimulating Factor
JF Pediatrics
JO Pediatrics
FD American Academy of Pediatrics
SP 392
OP 397
DO 10.1542/peds.105.2.392
VO 105
IS 2
A1 Calhoun, Darlene A.
A1 Lunøe, Mathilde
A1 Du, Yan
A1 Hutson, Alan D.
A1 Veerman, Mark
A1 Christensen, Robert D.
YR 2000
UL http://pediatrics.aappublications.org/content/105/2/392.abstract
AB 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 μg/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.Speculation. 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.