PHARMACOKINETICS OF INTRAVENOUS RECOMBINANT HUMAN GRANULOCYTE-COLONY-STIMULATING FACTOR (RHG-CSF) IN CHILDREN RECEIVING MYELOSUPPRESSIVE CANCER-CHEMOTHERAPY - CLEARANCE INCREASES IN RELATION TO ABSOLUTE NEUTROPHIL COUNT WITH REPEATED DOSING

Limited evidence suggests increased efficacy of rhG-CSF by subcutaneou s (SQ) compared with intravenous (IV) administration. To examine the p ossibility that rapid elimination of IV rhG-CSF could substantially sh orten the duration of systemic exposure and could explain a difference in pharmacodynamics, we characterized the pharmacokinetic profile of IV rhG-CSF for comparison to that previously reported for so administr ation. Twelve children were randomly assigned to receive 10 or more da ys of IV rhG-CSF at dosages of 5 or 10 mu g/kg a day beginning 24 hr a fter chemotherapy. Enzyme-linked immunosorbent assay (ELISA) was used to measure rhG-CSF concentrations in timed serum samples on days 1 and 10. Pharmacokinetic parameters were estimated by nonlinear, least squ ares regression. All serum concentration-time profiles were best descr ibed by a two-compartment model of elimination. Mean t(1/2 beta) value s ranged from 3.68 +/- 0.86 to 22.4 +/- 12.0 hr. ANC was correlated wi th log CL(T) (r = 0.72, P < 0.05), and inversely with log dose-adjuste d AUC (r = -0.75, P < 0.05) and log dose-adjusted C-max (r = -0.65, P < 0.05). Estimated duration of serum rhG-CSF concentrations above 1 ng /ml exceeded 24 hr for all but the 5 mu g/kg cohort on day 1. Pharmaco kinetic parameters of IV rhG-CSF are similar to those previously repor ted for so administration in children treated with myelosuppressive ca ncer chemotherapy. Daily IV administration should be a suitable altern ative route of administration in this patient population. (C) 1997 Wil ey-Liss, Inc.