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 (CLss) 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: CLss 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). CLss in these rats, at a low infusion rate was 95 ml/hr/kg, 14% lower than in control rats. The saturable CLss in these rats, 68 ml/hr/kg, was not significantly different from control rats (75 ml/hr/kg, p > 0.05). Also, CLss in cisplatin-treated rats with extensive renal failure, at a high infusion rate, decreased to 57% of controls. Furthermore, the total body clearances (CLtot) 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.
PURPOSE: To clarify the role of the kidney in the elimination of a recombinant humangranulocyte colony-stimulating factor, nartograstim, we have investigated its pharmacokinetics in rats with renal failure. METHODS: The steady-state clearance (CLss) 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: CLss 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). CLss in these rats, at a low infusion rate was 95 ml/hr/kg, 14% lower than in control rats. The saturable CLss in these rats, 68 ml/hr/kg, was not significantly different from control rats (75 ml/hr/kg, p > 0.05). Also, CLss in cisplatin-treated rats with extensive renal failure, at a high infusion rate, decreased to 57% of controls. Furthermore, the total body clearances (CLtot) 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.
Authors: T Kuga; Y Komatsu; M Yamasaki; S Sekine; H Miyaji; T Nishi; M Sato; Y Yokoo; M Asano; M Okabe Journal: Biochem Biophys Res Commun Date: 1989-02-28 Impact factor: 3.575
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