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Clinical pharmacology of filgrastim following high-dose chemotherapy and autologous bone marrow transplantation.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 1997 May; Vol. 3 (5), pp. 705-11. - Publication Year :
- 1997
-
Abstract
- We evaluated the pharmacokinetics and pharmacodynamics of filgrastim during a Phase I study of this cytokine following high-dose chemotherapy and autologous bone marrow transplantation. Serum granulocyte colony-stimulating factor concentrations were determined by ELISA in 21 patients receiving 14-day continuous i.v. filgrastim infusions and 10 patients receiving daily 4-h infusions. Models were developed for filgrastim systemic clearance (Cls) by incorporation of receptor-binding theory. Mean plasma half-life (t1/2) in the 4-h infusion group was 197 min, and the volume of distribution approximated plasma volume. WBC counts transiently fell, then rebounded immediately postinfusion, which correlated with a delay in the disappearance of serum granulocyte colony-stimulating factor. The effect of WBC concentrations on filgrastim Cls was determined in patients receiving continuous infusions by segregation of study periods based on the presence of severe neutropenia. Clearance increased in all 14 patients receiving doses of 4-32 microgram/kg/day during WBC recovery. The effect of WBCs on Cls was described by a differential equation that included a static component and one component that varied with WBC concentration. These data suggest that currently used filgrastim dosing strategies following autologous bone marrow transplantation may be suboptimal.
- Subjects :
- Adult
Antineoplastic Combined Chemotherapy Protocols adverse effects
Carmustine administration & dosage
Cisplatin administration & dosage
Combined Modality Therapy
Cyclophosphamide administration & dosage
Female
Filgrastim
Granulocyte Colony-Stimulating Factor adverse effects
Granulocyte Colony-Stimulating Factor pharmacokinetics
Humans
Leukocyte Count drug effects
Metabolic Clearance Rate
Recombinant Proteins
Regression Analysis
Transplantation, Autologous
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Bone Marrow Transplantation adverse effects
Breast Neoplasms therapy
Granulocyte Colony-Stimulating Factor therapeutic use
Melanoma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 3
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 9815739