title: Effects of renal function on pharmacokinetics of recombinant human granulocyte colony-stimulating factor in lung cancer patients.
abstract: Animal studies suggest that the kidney is involved in the elimination of recombinant human granulocyte colony-stimulating factor (rhG-CSF), which is used for patients with neutropenia during cancer chemotherapy. Since anticancer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study was designed to evaluate the relationship between the pharmacokinetics of rhG-CSF and renal function in lung cancer patients compared to the absolute neutrophil count (ANC). The pharmacokinetic studies were conducted with 25 lung cancer patients. Following chemotherapy using platinum-based compounds, a bolus 5 microg of rhG-CSF/kg of body weight was intravenously injected from the first day of leukopenia or neutropenia. Pharmacokinetic parameters were estimated by fitting the concentration in serum-time data to a two-compartment model according to the population pharmacokinetics and the Bayesian method. Creatinine clearance (CL(CR)) was predicted by the Cockcroft-Gault formula. rhG-CSF clearance (CL(G-CSF)) correlated significantly with the ANC (r = 0.613; P < 0.001) and CL(CR) (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination of the ANC and CL(CR) accounted for 57.4% of the variation of CL(G-CSF). In patients with an ANC of <1,000/microl, CL(CR) accounted for 72.9% of the variation of CL(G-CSF) (P < 0.001). Our findings suggest that renal function and neutrophil counts correlate with CL(G-CSF) and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: Y
authors.initials: Y
authors.lastname: Ishida
authors.forename: H
authors.initials: H
authors.lastname: Kinoshita
authors.forename: K
authors.initials: K
authors.lastname: Terashi
authors.forename: M
authors.initials: M
authors.lastname: Fukuda
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
authors.forename: A
authors.initials: A
authors.lastname: Kinoshita
authors.forename: H
authors.initials: H
authors.lastname: Soda
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000493:pharmacokinetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007677:Kidney Function Tests; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000493:pharmacokinetics
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor