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.
D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000633:toxicity*; D001772:Blood Cell Count; D001835:Body Weight / Q000187:drug effects; D004032:Diet; D004285:Dogs; D004334:Drug Administration Schedule; D004562:Electrocardiography; D005260:Female; D005449:Fluorenes / Q000633:toxicity*; D000882:Haplorhini; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity
D000889:Anti-Arrhythmia Agents; D005449:Fluorenes; C042398:indecainide; D000469:Alkaline Phosphatase