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 mg/kg intrav enously once daily for 3 to 5 days. Serum and urine samples were obtained b efore 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 infecte d but likely had hyporegenerative neutropenia (4 were born after pregnancy- induced hypertension/intrauterine growth restriction, and 1 had Rh hemolyti c disease). Five other infants (group 2) had neutropenia accompanying bacte rial sepsis and shock. Before receiving the first dose of rG-CSF, endogenou s G-CSF serum and urine concentrations were relatively low in group 1, aver aging 130 pg/mL (range: 48-209) in serum and 53 pg/mL (range: 15-141) in ur ine. Serum concentrations immediately before the final dose were much highe r (range: 81-24 835 pg/mL), whereas urine concentrations were unchanged (ra nge: <7 pg/mL-126 pg/mL). In group 2 patients, before receiving the first-d ose of rG-CSF, endogenous concentrations were very high, averaging 59 575 p g/mL (range: 20 028-98 280) in serum and 3189 pg/mL (range: 23-4770) in uri ne. Predose serum concentrations before the final dose (range: 427-14 460 p g/mL) were lower than before the first dose. The area under the concentrati on curve after the first dose of rG-CSF administration in group 1 was signi ficantly lower than after the first dose in group 2, but no difference in a rea 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 sat urable 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 fi rst 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-CS F, treatment with rG-CSF will add little or nothing to the neonates with se ptic shock and neutropenia are unlikely to derive benefit from rG-CSF admin istration.