Toxicology of indecainide hydrochloride after intravenous administration to rats and dogs

George E. Sandusky, Donald B. Meyers

Research output: Contribution to journalArticle

Abstract

Subchronic 1-month intravenous toxicity studies on indecainide, an antidysrhythmic agent, were conducted in rats and dogs. Rats (10 males, 10 females/group) were given daily intravenous (i.v.) doses of 0, 3, 6, or 9 mg/kg of indecainide for 1 month. 6 Of 10 males and 1 of 10 females given 9 mg/kg died during the test period. All but 2 animals from the other test groups survived. The high end of these daily doses was close to the acute single lethal dose, and the deaths were not unexpected. There were no treatment-related hematologic or serum chemistry changes in the surviving animals. No treatment-related histopathologic changes occurred in any of the animals. Groups of dogs (2 males, 2 females per group) were given daily i.v. injections of 0, 1.5, 3, or 4.5 mg/kg of indecainide for 1 month. 2 Of 4 dogs died after receiving multiple daily doses of 4.5 mg/kg. No treatment-related histopathologic changes were present in these animals. Dogs given doses of 1.5. or 3 mg/kg tolerated daily injections of the compound with no overt signs of toxicity and without hematologic, serum chemistry or histologic changes. Electrocardiograms revealed prolonged PR, QRS, and QT intervals in dogs from all three dose groups. Rats and dogs tolerated daily intravenous doses of indecainide as high as 6 and 3 mg/kg, respectively, with no evidence of any effect of treatment except the expected pharmacological action on the myocardium.

Original languageEnglish (US)
Pages (from-to)107-110
Number of pages4
JournalToxicology Letters
Volume26
Issue number2-3
DOIs
StatePublished - Aug 1985

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Keywords

  • Indecainide
  • dogs
  • rats

ASJC Scopus subject areas

  • Toxicology

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