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.

FIG. 1

Correlation between rhG-CSF clearance and circulating neutrophil counts (top) and creatinine clearance (bottom).

FIG. 2

Relationship between actual rhG-CSF clearance and estimated rhG-CSF clearance based on the multiple linear regression equation CL_G-CSF (liter/h) = 0.008 CL_CR (ml/min) + 0.352 log ANC (per μl) − 0.809.

FIG. 3

Relationship between rhG-CSF clearance and creatinine clearance in patients with neutrophil counts of <1,000/μl.