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Antimicrobial Agents and Chemotherapy, July 2001, p. 1947-1951, Vol. 45, No. 7
Second Department of Internal Medicine,
Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki
852-8501,1 Division of Molecular and
Clinical Microbiology, Department of Molecular Microbiology and
Immunology, Nagasaki University Graduate School of Medical
Sciences, 1-12-4 Sakamoto, Nagasaki
852-8523,2 Clinical Pharmacology
Section, Clinical Research Coordination Department, Chugai
Pharmaceutical Co., 2-1-9 Kyobashi, Chuo-ku, Tokyo
104-8301,3 Internal Medicine,
Nagasaki-Chuo National Hospital, 2-1001-1 Kubara, Omura, Nagasaki
856-0835,4 and Department of Laboratory
Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto,
Nagasaki 852-8501,5 Japan
Received 14 August 2000/Returned for modification 13 January
2001/Accepted 29 March 2001
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 µg 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
(CLCR) was predicted by the Cockcroft-Gault formula.
rhG-CSF clearance (CLG-CSF) correlated significantly with
the ANC (r = 0.613; P < 0.001) and
CLCR (r = 0.632; P < 0.001). Multiple linear regression analysis showed that the combination
of the ANC and CLCR accounted for 57.4% of the variation
of CLG-CSF. In patients with an ANC of <1,000/µl, CLCR accounted for 72.9% of the variation of
CLG-CSF (P < 0.001). Our findings suggest
that renal function and neutrophil counts correlate with
CLG-CSF and that the role of renal function in eliminating
rhG-CSF is important in lung cancer patients with neutropenia.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.7.1947-1951.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Effects of Renal Function on Pharmacokinetics of
Recombinant Human Granulocyte Colony-Stimulating Factor in Lung
Cancer Patients
*
Corresponding author. Mailing address: Second
Department of Internal Medicine, Nagasaki University School of
Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Phone: 81 (95)
849-7274. Fax: 81 (95) 849-7285. E-mail:
soda{at}net.nagasaki-u.ac.jp.
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