Subchronic and chronic toxicity of the new sulfonylurea glimepiride in dogs

The new sulfonylurea glimepiride (Hoe 490, CAS 93479-97-1) was tested in subchronic and chronic toxicity studies in dogs. Up to and including a dose of 16 mg/kg b.w. neither toxic effects nor pathological changes were observed in the treated animals. Also at a dose of 320 mg/kg b.w. which was applied over a period of 6 months no undesired effects were detected. However, after a treatment period of 1 year in some of the animals which received 320 mg/kg b.w. cataract formation appeared. The mechanism for that still remains unclear but is not due to changes in special biochemical reactions as it can be observed with other typical cataractogenic chemicals. The relevance of these findings for the application of that drug in humans therefore has to be discussed bearing in mind the extremely high dose and serum levels as well as the number of animals (2/12) where the effects were seen. As expected in all experiments pharmacodynamic effects like reduced serum glucose levels and a degranulation of the beta-cells of the pancreas were seen. Both effects were completely reversible within the recovery period.