Four-week sub-acute toxicity study 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 (DR-3355) in CD rats and cynomolgus monkeys.

Abstract

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, DR-3355, a new quinolone antimicrobial agent, was administered by oral gavage to groups of ten male and ten female CD rats at dosages of 50, 200 or 800 mg/kg/day and to groups of three male and three female cynomolgus monkeys at dosages of 10, 30, or 100 mg/kg/day. Both species were treated for four weeks. The vehicle (0.5% sodium carboxymethyl cellulose)-treated group served as control. Rats at the high dose showed salivation, slight increases in total leucocyte and lymphocyte counts, slight changes in the plasma electrolyte balance, and minor reductions in urea concentration. The articular surfaces of the humerus and femur of rats at the high dose showed minor degenerative changes. Increased caecal weight occurred in rats at all the treatment groups. Monkeys at the high dose showed salivation, diarrhoea and lost weight. There was no microscopic change in the tissues examined. No effect levels under these conditions were established at 200 mg/kg/day in the rat, and 30 mg/kg/day in the monkey.