Acute oral toxicity of the new quinolone antibacterial agent levofloxacin in mice, rats and monkeys.

Acute oral toxicity of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazinyl)-7-oxo-7H-pyrido [1,2,3-de][1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4), a new quinolone antibacterial agent, was studied in ddy mice, SD rats and cynomolgus monkeys. LD50 values were 1,881 mg/kg for males and 1,803 mg/kg for females in mice, 1,478 mg/kg for males and 1,507 mg/kg for females in rats and more than 250 mg/kg in females monkeys. Toxic signs included the decrease in locomotor activity, ptosis, tremor, tonic convulsion and respiratory depressed in rodents and soft feces or vomiting in monkeys. At necropsy, no treatment-related changes were observed in any species except for the enlargement of the cecum in rats.