Abstract
4-week repeated dose toxicity study with 4-week recovery test of sodium N-[2-[4-(2, 2-dimethylpropionyloxy)phenylsulfonylamino]benzoyl]aminoacetate tetrahydrate(ONO-5046·Na), a novel neutrophil elastase inhibitor, was conducted in beagle dogs. The dogs of both sexes were administered ONO-5046·Na intravenously at a daily dose of 0(vehicle control), 7.5, 15 or 30 mg/kg. In the 15 mg/kg female group and the 30 mg/kg male and female groups, transient hypoactivity and ataxic gait were observed. It is considered that these symptoms were attributed to the pharmacological effect of ONO-5046·Na. Also, in the 30 mg/kg male and female groups, erythrocyte, hematocrit and hemoglobin were decreased.In the 30 mg/kg male group, lung weight was increased. However, histopathological examination revealed there were no changes in any organs including the lungs. There were no treatment-related changes in body weights, food consumption, opthalmology, occult blood in feces, urinalysis, blood chemistry, electrocardiography, blood pressure, temperature, pulse rate, hepatic and renal function or necropsy. These results indicate that the NOAEL of ONO-5046·Na in dogs is 15 mg/kg/day for both sexes in this study.
