Renal clearance of a recombinant granulocyte colony-stimulating factor, nartograstim, in rats.
OBJECTIVE
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.
Kuwabara
T
T
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Ishikawa
Y
Y
Kobayashi
H
H
Kobayashi
S
S
Sugiyama
Y
Y
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology; D005919:Glomerular Filtration Rate; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007444:Inulin / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D051437:Renal Insufficiency / Q000503:physiopathology; D010130:p-Aminohippuric Acid / Q000493:pharmacokinetics
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D007444:Inulin; C072115:nartograstim; D002945:Cisplatin; D010130:p-Aminohippuric Acid