Comparative study of increased plasma quinidine concentration in rats with glycerol- and cisplatin-induced acute renal failure

Yuki Izuwa, Jun Ichi Kusaba, Mizuki Horiuchi, Tetsuya Aiba, Hiromu Kawasaki, Yuji Kurosaki

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19 Citations (Scopus)

Abstract

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 a1-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.

Original languageEnglish
Pages (from-to)451-457
Number of pages7
JournalDrug metabolism and pharmacokinetics
Volume24
Issue number5
DOIs
Publication statusPublished - Jan 1 2009

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Keywords

  • Acute renal failure
  • Cisplatin
  • Glycerol
  • Quinidine
  • α-acid glycoprotein

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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