Comparative study of increased plasma quinidine concentration in rats with glycerol- and cisplatin-induced acute renal failure.
A comparative study of altered plasma concentration of quinidine in rats with glycerol- and cisplatin-induced acute renal failure (ARF) was conducted with quinidine used as a positively charged and liver-metabolized therapeutic compound. Although apparent total body clearance of quinidine decreased to 68 and 48% of the normal value in glycerol- and cisplatin-induced ARF rats, respectively, its distribution decreased only in glycerol-induced ARF rats. The plasma unbound fraction of quinidine decreased in glycerol-induced ARF rats, which was not observed in cisplatin-induced ARF rats. The plasma level of alpha(1)-acid glycoprotein (AGP) increased in glycerol-induced ARF, but not in cisplatin-induced ARF rats. It is therefore conceivable that the plasma concentration of positively charged and liver-metabolized compounds generally increases due to hepatic elimination suppressed as renal function decreases, but the pharmacokinetic impact of suppressed hepatic elimination is occasionally difficult to observe in some ARF model rats since it may be blurred by the influence of increased plasma AGP level.
Izuwa
Yuki
Y
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Kusaba
Jun-ichi
J
Horiuchi
Mizuki
M
Aiba
Tetsuya
T
Kawasaki
Hiromu
H
Kurosaki
Yuji
Y
D058186:Acute Kidney Injury / Q000097:blood* / Q000139:chemically induced; D000818:Animals; D002945:Cisplatin; D005990:Glycerol; D008297:Male; D009961:Orosomucoid / Q000378:metabolism; D011485:Protein Binding; D011802:Quinidine / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000493:pharmacokinetics
D009961:Orosomucoid; D014044:Tolbutamide; D011802:Quinidine; D005990:Glycerol; D002945:Cisplatin