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

✍ Scribed by Sturgill, Marc G.; Huhn, Richard D.; Drachtman, Richard A.; Ettinger, Alice G.; Ettinger, Lawrence J.

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 122 KB
• Volume: 54
• Category: Article
• ISSN: 0361-8609
• DOI: 10.1002/(sici)1096-8652(199702)54:2<124::aid-ajh5>3.0.co;2-z

✦ Synopsis

Limited evidence suggests increased efficacy of rhG-CSF by subcutaneous (SQ) compared with intravenous (IV) administration. To examine the possibility that rapid elimination of IV rhG-CSF could substantially shorten 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 SQ administration. Twelve children were randomly assigned to receive 10 or more days of IV rhG-CSF at dosages of 5 or 10 g/kg a day beginning 24 hr after 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 squares regression. All serum concentration-time profiles were best described by a two-compartment model of elimination. Mean t 1/2␤ values ranged from 3.68 ؎ 0.86 to 22.4 ؎ 12.0 hr. ANC was correlated with log CL T (r ‫؍‬ 0.72, P Ͻ 0.05), and inversely with log dose-adjusted AUC (r ‫؍‬ Ϫ0.75, P Ͻ 0.05) and log dose-adjusted C max (r ‫؍‬ ؊0.65, P Ͻ 0.05). Estimated duration of serum rhG-CSF concentrations above 1 ng/ml exceeded 24 hr for all but the 5 g/kg cohort on day 1. Pharmacokinetic parameters of IV rhG-CSF are similar to those previously reported for SQ administration in children treated with myelosuppressive cancer chemotherapy. Daily IV administration should be a suitable alternative route of administration in this patient population. Am.