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Antimicrobial Agents and Chemotherapy, July 2001, p. 1947-1951, Vol. 45, No. 7
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

Masaaki Fukuda,1 Mikio Oka,2 Yoshimasa Ishida,3 Haruki Kinoshita,3 Kenji Terashi,1 Minoru Fukuda,1 Shigeru Kawabata,1 Akitoshi Kinoshita,4 Hiroshi Soda,1,5,* and Shigeru Kohno1,2

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.


* 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.


Antimicrobial Agents and Chemotherapy, July 2001, p. 1947-1951, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.1947-1951.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.