Acute, subchronic, and chronic toxicity of ecadotril in dogs

Objective-To determine the toxicity of ecadotril in dogs. Animals-74 healthy 4- to 11-month-old Beagles. Procedure-To determine acute toxicity ecadotril (2,000 mg/kg of body weight , PO) in a gelatin capsule was administered once to 2 dogs, and dogs were o bserved for 2 weeks. To determine subchronic and chronic toxicity, ecadotri l was administered every day for 3 months (50 mg/kg [n = 8], 100 mg/kg [8], 300 mg/kg [12]) and 12 months (25 mg/kg [n = 8]. 50 mg/kg [8], 100 mg/kg [ 8]), respectively. Dogs in control groups (n = 12 or 8) received an empty g elatin capsule. Physical examinations, CBC, plasma biochemical analyses, an d urinalyses were performed before and at various times during each experim ent. Dogs were euthanatized at the end of each experiment, and necropsies w ere performed. Results-Dogs that received 1 dose of 2,000 mg of ecadotril/kg developed non specific clinical signs of toxicosis. Dogs that received 300 mg of ecadotri l/kg/d for 3 months developed pronounced anemia, bone marrow suppression, a nd some evidence of liver impairment. There was no evidence of an effect ac cumulated over time, and reversibility of toxic effects was evident. Dogs t hat received less than or equal to 100 mg of ecadotril/kg/d for 3 or 12 mon ths tolerated treatment without apparent effect. Conclusions and Clinical Relevance-Degree of acute toxicity of a single hig h dose of ecadotril in dogs was low. The no-observable adverse effect level of ecadotril following daily oral administration was 100 mg/kg/d; repeated administration of 300 mg/kg/d revealed the hematopoietic system as the pri mary toxicologic target.