Effects of renal function on pharmacokinetics of recombinant human granulocyte colony-stimulating factor in lung cancer patients

Animal studies suggest that the kidney is involved in the elimination of re combinant human granulocyte colony-stimulating factor (rhG-CSF), which is u sed for patients with neutropenia during cancer chemotherapy. Since antican cer drugs induce nephrotoxicity, it is important to clarify the role of the kidney in the pharmacokinetics of rhG-CSF in cancer patients. Our study wa s designed to evaluate the relationship between the pharmacokinetics of rhG -CSF and renal function in lung cancer patients compared to the absolute ne utrophil count (ANC). The pharmacokinetic studies were conducted with 25 lu ng cancer patients. Following chemotherapy using platinum based compounds, a bolus 5 mug 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-compart ment model according to the population pharmacokinetics and the Bayesian me thod. Creatinine clearance (CLCR) was predicted by the Cockcroft-Gault form ula. rhG-CSF clearance (CLG-CSF) correlated significantly with the ANC (r = 0.613; P < 0.001) and C-CR (r = 0.632; P < 0.001). Multiple linear regress ion 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/<mu>l, CLCR accounted for 72.9% of the variation of CLG-CSF (P < 0.001). Our find ings suggest that renal function and neutrophil counts correlate with CLG-C SF and that the role of renal function in eliminating rhG-CSF is important in lung cancer patients with neutropenia.