Toxicology of indecainide hydrochloride in mice, rats, and dogs

Indecainide is a new (investigational) drug for treating cardiac arrhythmias. When given orally to either young adult rats or mice, the LD50 was ca. 100 mg/kg. Leg weakness, tremors, and occasional convulsions were seen in rodents given doses in the lethal range. Dogs and monkeys survived a single oral dose of 25 mg/kg; however, there was a pronounced increase in duration of the PR and QRS intervals. In a 3-month subchronic toxicity study, rats fed dietary levels equivalent to 20 mg/kg/day indecainide were unaffected. Body weight gain was slightly depressed in both sexes of the 40-mg/kg dose group and moderately reduced in both sexes of the 85-mg/kg dose group. Alkaline phosphatase values were minimally increased in females of the 85-mg/kg dose group. In a 3-month subchronic toxicity study, dogs were given daily doses of 0, 6.25, 12.5, or 25 mg/kg indecainide. One male in the 12.5-mg/kg dose group and two females in the 25-mg/kg dose group died during the study. EKG recordings showed a prolongation of the PR and QRS intervals in all treated dogs. In addition, there was a notch in or just prior to the R wave. There were no histopathology findings related to treatment in rats and dogs in the 3-month subchronic rat and dog studies.