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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 observed for 2 weeks. To determine subchronic and chronic toxicity, ecadotril 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 gelatin capsule. Physical examinations, CBC, plasma biochemical analyses, and urinalyses were performed before and at various times during each experiment. Dogs were euthanatized at the end of each experiment, and necropsies were performed.


RESULTS
Dogs that received 1 dose of 2,000 mg of ecadotril/kg developed nonspecific clinical signs of toxicosis. Dogs that received 300 mg of ecadotril/kg/d for 3 months developed pronounced anemia, bone marrow suppression, and some evidence of liver impairment. There was no evidence of an effect accumulated over time, and reversibility of toxic effects was evident. Dogs that received < or =100 mg of ecadotril/kg/d for 3 or 12 months tolerated treatment without apparent effect.


CONCLUSIONS AND CLINICAL RELEVANCE
Degree of acute toxicity of a single high 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 primary toxicologic target.