One-month oral toxicity study of the new quinolone antibacterial agent (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6-yl)-9-fluoro-2,3-dihydro-3- methyl-7-oxo-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylic acid hemihydrate in rats and cynomolgus monkeys.
One-month oral toxicity of (S)-10-[(S)-(8-amino-6-azaspiro[3,4] octan-6-yl)]-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent was investigated in Sprague-Dawley rats at doses of 12.5, 50, 200 and 800 mg/kg/d and in cynomolgus monkeys at 10, 30 and 100 mg/kg/d. Rats receiving 200 mg/ kg showed abnormal urine crystals, enhanced deposition of lipid in hepatocytes and exacerbation of osteochondrotic lesions in the femoral condyle. In addition, dosing at 800 mg/kg induced decrease in body weight gain and increased levels of serum alkaline phosphatase (ALP), cholinesterase, leucine aminopeptidase and total cholesterol. Monkeys receiving 100 mg/kg showed abnormal urine crystals and increases in serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and ALP levels. The non-toxic doses of DV-7751a in rats and monkeys were 50 and 30 mg/kg, respectively, under the present experimental conditions.