Effects of hypokalaemia on arrhythmogenic risk of quinidine in rats

Michiko Hirota, Hisakazu Ohtani, Erika Hanada, Hajime Kotaki, Yasufumi Sawada, Tatsuji Iga

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Plasma potassium concentration plays an important role in the induction of arrhythmia and is closely related to the arrhythmogenicity of various drugs. We quantitatively analyzed the influence of plasma potassium concentration on QT intervals before drug administration and on drug-induced QT prolongation, to estimate the risk of drug-induced arrhythmia under hypokalaemic conditions. The hypokalaemic models were produced by intraperitoneal administration of furosemide and hydrochlorothiazide in male Sprague-Dawley rats. The relationship between the changes in QT intervals and time profiles of plasma quinidine (QND) concentration were analyzed during constant intravenous infusion of QND (10 or 30 mg/kg/h) and post infusion in normal and hypokalaemic rats. The plasma QND concentration reached the therapeutic range (3-7 μg/ml) at the high infusion rate (30 mg/kg/h). No pharmacokinetic differences between normal and hypokalaemic rats were observed. QND induced QT prolongation in parallel with the plasma concentration without hysteresis. Although the potency of QND for QT prolongation was not affected by hypokalaemia, the QT intervals before drug administration were significantly prolonged in hypokalaemic rats (65.90 ± 1.40 vs 56.60 ± 0.748 msec, mean ± SEM, p < 0.0001). Thus, the prolongation of QT intervals before drug administration may act as a risk factor of arrhythmia under hypokalaemic conditions.

Original languageEnglish
Pages (from-to)2159-2169
Number of pages11
JournalLife Sciences
Volume62
Issue number24
DOIs
Publication statusPublished - 1998 May 8

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Keywords

  • Arrhythmia
  • Electrocadiography
  • Hypokalaemia
  • Potassium
  • QT interval
  • Quinidine

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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