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

被引:24
作者
Calhoun, DA
Lunoe, M
Du, Y
Hutson, AD
Veerman, M
Christensen, RD
机构
[1] Univ Florida, Coll Med, Dept Pediat, Div Neonatol, Gainesville, FL 32610 USA
[2] Univ Florida, Coll Med, Clin Res Ctr, Gainesville, FL 32610 USA
[3] Shands Teaching Hosp, Dept Pharm Practice, Gainesville, FL USA
关键词
granulocyte colony-stimulating factor; neonates; neutrophils; pharmacokinetics;
D O I
10.1542/peds.105.2.392
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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 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 neonates with septic shock and neutropenia are unlikely to derive benefit from rG-CSF administration.
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页码:392 / 397
页数:6
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