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

Am J Hematol. 1997 Feb;54(2):124-30. doi: 10.1002/(sici)1096-8652(199702)54:2<124::aid-ajh5>3.0.co;2-z.

Abstract

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 microg/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 t1/2beta values ranged from 3.68 +/- 0.86 to 22.4 +/- 12.0 hr. ANC was correlated with log CLT (r = 0.72, P < 0.05), and inversely with log dose-adjusted AUC (r = 0.75, P < 0.05) and log dose-adjusted Cmax (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 microg/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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / therapeutic use*
  • Bone Marrow / drug effects*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Granulocyte Colony-Stimulating Factor / blood
  • Granulocyte Colony-Stimulating Factor / pharmacokinetics*
  • Humans
  • Injections, Intravenous
  • Leukocyte Count
  • Male
  • Neutrophils / pathology*
  • Recombinant Proteins

Substances

  • Antineoplastic Agents
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor