Effects of Renal Function on Pharmacokinetics of Recombinant Human Granulocyte Colony-Stimulating Factor in Lung Cancer Patients

Open Access
Publisher Website
Google Scholar
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 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 CLCRaccounted for 57.4% of the variation of CLG-CSF. In patients with an ANC of CRaccounted for 72.9% of the variation of CLG-CSF(P< 0.001). Our findings suggest that renal function and neutrophil counts correlate with CLG-CSFand that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.