Subchronic toxicity of the new quinolone antibacterial agent irloxacin in beagle dogs

The subchronic oral toxicity of the new quinolone antibacterial agent irlox acin (6-fluorine-7-(pyrrol-1-yl)-l-ethyl-l,4-dihydro-4-oxo-quinolone-3-carb oxylic acid, CAS 91524-15-1) in Beagle dogs was investigated in studies of 4 and 29 weeks of duration. In both studies animals received dosages of 10, 120 and 1400 mg/kg/d. Pale coloured faeces were seen on animals receiving 1400 mg/kg/d. Animals r eceiving 1400 mg/kg/d for 29 weeks showed an increased incidence of wax in the ears during the latter half of the treatment period, and one male and o ne female experienced transitory locomotive difficulties at the end of the first week of treatment. The liver was identified as the target organ for t oxicity with presence of lipofuscin in the hepatocytes of animals receiving 120 or 1400 mg/kg/d for 29 weeks. Slight increases in liver weights were o bserved in animals receiving 120 or 1400 mg/kg/d for 4 weeks, and in all gr oups receiving irloxacin for 29 weeks. However, no histopathological findin gs were observed in the liver of animals receiving irloxacin for 4 weeks or those receiving 10 mg/kg/d for 29 weeks. Other relevant findings observed in the 29 week study were increased triglyceride, phospholipid and choleste rol levels in males receiving 120 mg/kg/d and animals receiving 1400 mg/kg/ d, increased albumin and decreased betaglobulin concentrations in females r eceiving 1400 mg/kg/d, and prolonged activated partial thromboplastin time in animals receiving 1400 mg/kg/d. On the basis of the results obtained it is concluded that 10 mg/kg/d can be considered as the non-toxic dose after 29 week oral administration of irloxacin in dogs.