Long-term tolerance of imidapril in the cat.

ABSTRACT

OBJECTIVES: To determine the long-term tolerance of imidapril HCl, a novel angiotensin-converting enzyme inhibitor (ACEi), after repeated administrations in the cat. BACKGROUND: ACEi's are the first-line treatment for congestive heart failure in small animals. They are believed to have potential protective effects on kidney, especially in cats. As they are used for chronic pathologies, their long-term tolerance has to be proven before clinical studies may be performed. METHODS: To determine chronic tolerance, 24 cats were administered 0.5, 1.5 or 5 mg/kg/day of imidapril or a placebo for 3 months. Cats were subjected to clinical examination, cardiovascular follow-up (ECG and blood pressure determination), haemato-biochemistry and urinalysis. A toxicokinetic follow-up was carried out, and a complete necropsy performed at the end of the study. RESULTS: After three months of administration, there were no clinical, cardiovascular, haemato-biochemical, or urinary adverse effect. At necropsy, cats from the high dose group (5 mg/kg/day) showed a slight hypertrophy of the juxtaglomerular apparatus with increased granulation. This was considered to be a pharmacological rather than a toxic effect. CONCLUSIONS: No sign of toxicity was seen during this study. As preclinical data suggested that pharmacodynamic effect in the cat was obtained with a posology of 0.5mg/kg/day, imidapril can be considered as perfectly safe for long-term administration in the cat.