Reproductive toxicity of the new quinolone antibacterial agent levofloxacin in rats and rabbits.

The reproductive 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) was investigated in rats and rabbits. DR-3355 was administered orally prior to and in the early stage of pregnancy to male and female rats at doses of up to 360 mg/kg. No adverse effects on fertility or teratogenicity were noted at any dose. DR-3355 elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats at doses of up to 810 mg/kg, or to pregnant rabbits at doses of up to 50 mg/kg. However, female rats receiving 810 mg/kg showed salivation, soiled coats, soft stools and decreases in body weight and food intake. Rat fetuses in the 810 mg/kg group exhibited decreased body weight and retardation of ossification, and showed increases in mortality and skeletal variations. Decreases in maternal body weight and food intake were observed in rabbits in the 50 mg/kg group. No adverse effects were observed in perinatal and postnatal toxicity studies in rats using doses of up to 360 mg/kg.