Renal Clearance of a Recombinant Granulocyte Colony-Stimulating Factor,Nartograstim, in Rats

Purpose. To clarify the role of the kidney in the elimination of a recombinant human granulocyte colony-stimulating factor, nartograstim, we have investigated its pharmacokinetics in rats with renal failure.Methods. The steady-state clearance (CL_ss) were determined by the intravenous infusion for 4 hr to unilateral renally-ligated and cisplatin-treated rats, whose renal functions were about 50 and 10 % of controls, respectively.Results. CL_ss of nartograstim (27 ml/hr/kg) in the renally-ligated rats at a high infusion rate was significantly lower (25%) than in control rats (p<0.05). CL_ss in these rats, at a low infusion rate was 95 ml/hr/kg, 14 % lower than in control rats. The saturable CL_ss in these rats, 68 ml/hr/kg, was not significantly different from control rats (75 ml/hr/kg, p>0.05). Also, CL_ss in cisplatin-treated rats with extensive renal failure, at a high infusion rate, decreased to 57 % of controls. Furthermore, the total body clearances (CL_tot) of nartograstim after bolus intravenous administration to renally-ligated and cisplatin-treated rats were reduced to 33–49 % of controls.Conclusions. These results suggest that the kidney may be responsible for 40– 50 % of the nonsaturable clearance of nartograstim. Thus, the kidney should make a major contribution to the elimination of nartograstim when rats are given a high dose of nartograstim, which saturates the receptor-mediated clearance.