Developmental toxicity studies of the quinolone antibacterial agent irloxacin in rats and rabbits

Embryotoxicity studies on irloxacin (6-fluorine-7-(pyrrol-1-yl)-1-ethyl-1,4-dihydro-4-oxo-quinolone-3-carboxylic acid, CAS-91524-15-1), a new fluoroquinolone antibacterial agent, were performed in rats and rabbits. Oral administration of irloxacin during the fetal period of organogenesis to pregnant rats and rabbits at dose levels of up to 1000 and 350 mg/kg/d, respectively, elicited no evidence of teratogenicity. During the first days of treatment, transient stasis in body weight increase was observed in rat dams receiving doses of 350 or 1000 mg/kg/d, and reduced food consumption was observed in those receiving 1000 mg/kg/d. Necropsy on day 20 of gestation showed dosage related increase in liver and kidney weights in all rat treated groups. Rabbit dams receiving 350 mg/kg/d showed during the first days of treatment decrease in body weight, and decreased food consumption and faecal output. Also, four females receiving 350 mg/kg/d aborted between days 18 and 20 of gestation. Rat fetuses in the 350 and 1000 mg/kg/d showed decreased body weight, and a decrease in placental weights was observed in the 1000 mg/kg/d group. No retardations or malformations were observed in rat or rabbit fetuses at any tested dose level. For maternal and embryo-fetal effects 100 and 150 mg/kg/d can be considered as the no-effect-level (NOEL) for rats and rabbits, respectively.