title: Levels of recombinant human granulocyte colony-stimulating factor in serum are inversely correlated with circulating neutrophil counts.
abstract: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is effective in countering chemotherapy-induced neutropenia. However, serum rhG-CSF levels cannot be maintained throughout the course of rhG-CSF therapy. The drop in serum rhG-CSF levels may vary with the duration of rhG-CSF administration or with the circulating neutrophil counts. We investigated the relationship between serum G-CSF levels and circulating neutrophil counts and the pharmacokinetics of rhG-CSF for patients with lung cancer who had been treated with myelosuppressive chemotherapy and then with subcutaneous rhG-CSF (lenograstim, 2 micrograms per kg of body weight per day). Twelve patients were randomly assigned to four groups with different rhG-CSF therapy schedules. Serum G-CSF levels were measured by an enzyme immunoassay method. Serum G-CSF levels during the rhG-CSF therapy greatly exceeded endogenous G-CSF levels and were mainly due to the presence of exogenous rhG-CSF rather than increased levels of endogenous G-CSF. Despite the duration of rhG-CSF administration, serum G-CSF levels during rhG-CSF therapy were inversely correlated with circulating neutrophil counts (r2 = 0.73, P < 0.0001). The value for the area under the concentration-time curve of rhG-CSF on the day of neutrophilia was lower than that on the day of neutropenia (P < 0.05). Our results suggest that the fall in serum G-CSF levels during rhG-CSF therapy may result from increased clearance and/or decreased absorption of rhG-CSF, two processes related to circulating neutrophil counts.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Nagasaki University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takatani
authors.forename: H
authors.initials: H
authors.lastname: Soda
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: A
authors.initials: A
authors.lastname: Kinoshita
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: M
authors.initials: M
authors.lastname: Oka
mesh_terms: D000368:Aged; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D007958:Leukocyte Count; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000097:blood*; D009504:Neutrophils; D011994:Recombinant Proteins / Q000097:blood
chemical_list: D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor