RGD Reference Report - Granulocyte colony-stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor. - Rat Genome Database

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Granulocyte colony-stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor.

Authors: Calhoun, DA  Lunoe, M  Du, Y  Hutson, AD  Veerman, M  Christensen, RD 
Citation: Calhoun DA, etal., Pediatrics. 2000 Feb;105(2):392-7.
RGD ID: 11039039
Pubmed: PMID:10654961   (View Abstract at PubMed)

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. 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neutropenia  IDA 11039039 RGD 
neutropenia  ISOCSF3 (Homo sapiens)11039039; 11039039 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Csf3  (colony stimulating factor 3)

Genes (Mus musculus)
Csf3  (colony stimulating factor 3 (granulocyte))

Genes (Homo sapiens)
CSF3  (colony stimulating factor 3)


Additional Information