Pharmacokinetics and pharmacodynamics following intravenous administration of recombinant human hepatocyte growth factor in rats with renal injury.
OBJECTIVE
Hepatocyte growth factor (HGF) plays a role in the regeneration and protection of the kidney, but little information is available concerning the pharmacokinetics of therapeutic treatment with HGF. In this study, HGF was administered after the onset of renal injury, and pharmacokinetic analysis was performed simultaneously with an efficacious dose.


METHODS
For the study of pharmacodynamics, recombinant human HGF was intravenously administered to rats with glycerol-induced acute kidney injury (AKI). In the pharmacokinetic study, rats subjected to glycerol injection or renal ischemia-reperfusion were used as models of AKI, and rats subjected to 5/6 nephrectomy were used as models of chronic kidney disease (CKD).


RESULTS
After intravenous administration of HGF at doses of 0.5-2.0 mg/kg, the elevation of blood urea nitrogen was suppressed, indicating that HGF had a pharmacodynamic effect. However, no significant difference was seen in the pharmacokinetic parameters such as clearance, distribution volume and half-life between the normal, AKI and CKD groups.


CONCLUSIONS
The intravenous administration of HGF after the onset of renal dysfunction exerted a pharmacological effect on AKI, and renal injury did not affect the clearance of plasma HGF. This unaffected profile may serve as a base for the safety of HGF during therapeutic administration.
Division of Tumor Dynamics and Regulation, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Eri
E
Adachi
Tomoko
T
Hirose-Sugiura
Yukio
Y
Kato
Fumie
F
Ikebuchi
Atsuko
A
Yamashita
Tetsushi
T
Abe
Kazuhiro
K
Fukuta
Kiichi
K
Adachi
Kunio
K
Matsumoto
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001806:Blood Urea Nitrogen; D005990:Glycerol; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D007275:Injections, Intravenous; D007668:Kidney / Q000473:pathology; D008297:Male; D009392:Nephrectomy; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D015427:Reperfusion Injury
C066855:HGF protein, human; D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor; D005990:Glycerol