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Pharmacokinetics of subcutaneous recombinant human granulocyte colony-
stimulating factor in children
N Stute, VM Santana, JH Rodman, MJ Schell, JN Ihle and WE Evans
Pharmaceutical Division, St Jude Children's Research Hospital, Memphis
38101.
Fifteen children (age 1.2 to 9.4 years) with advanced neuroblastoma were
treated with myelosuppressive chemotherapy (cyclophosphamide, cisplatin,
doxorubicin) followed by 5 (n = 5), 10 (n = 5), or 15 (n = 5) micrograms/kg
recombinant granulocyte colony-stimulating factor (rG- CSF) subcutaneously
(SC) once daily for 10 days, starting the day after chemotherapy. Serial
serum samples obtained on days 1 and 10 were analyzed for G-CSF activity by
a specific proliferation assay using NFS- 60 cells. G-CSF serum
concentration-time data were best described by a one-compartment model,
with zero-order absorption and first-order elimination. After SC injection,
absorption was prolonged, with peak concentrations of G-CSF (3 to 117
ng/mL) being reached after 4 to 12 hours. The relatively slow absorption,
with a mean elimination half- life of 5.8 hours on day 1 and 4.5 hours on
day 10, provided measurable G-CSF concentrations for the entire 24-hour
dosing interval in all patients at each dosage level. The median apparent
clearance of G-CSF on day 10 was significantly higher than on day 1 (0.57 v
0.31 mL/min/kg, P = .02), and was positively correlated with the absolute
neutrophil count (ANC) (r2 = .33, P = .003). Systemic exposure to G-CSF was
dose-related, but interpatient pharmacokinetic variability yielded overlap
in area under the concentration-time curve (AUC) at all three dosage
levels. Stepwise regression analysis showed that G-CSF AUC could be
predicted by a model that includes rG-CSF dosage and ANC on the day of
administration (r2 = .82, P = .0001).
Volume 79,
Issue 11,
pp. 2849-2854,
06/01/1992
Copyright © 1992 by The American Society of Hematology
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