Acute and subchronic toxicity studies of the new quinolone antibacterial agent irloxacin in rodents

Irloxacin (6-fluorine-7-(pyrrol-1-yl)-1-ethyl-1,4-dihydro-4-oxo-quinolone-3 -carboxylic acid, CAS 91524-15-1), a new quinolone antibacterial agent, was administered as a single dose to rats and mice both by oral and intraperit oneal route in oder to study its acute toxicity. Its oral subchronic tocixi ty was also assessed by treating rats for 4 and 13 weeks. The results obtai ned showed that irloxacin was well tolerated after single administration in mice and rats, with LD50 values above 2000 and 5000 mg/kg for intraperiton eal and oral administration, respectively. In the oral subchronic toxicity studies, the histopathological examination performed after the 13-week trea tment period confirmed the kidney as the target organ for toxicity. Increas ed presence of lipofuscin in the kidneys was observed in animals receiving 2000 or 450 mg/kg/d, and degeneration and/or dilatation of proximal renal t ubules and chronic interstitial nephritis in males receiving these dosages. No histopathological findings were observed in the kidneys of animals rece iving 100 mg/kg/d for 13 weeks. Other relevant findings were, presence of d ark or cloudy urine with slightly lower pH in animals receiving dosages of 450 mg/kg/d and above, increased urinary protein concentration in animals r eceiving 2000 or 450 mg/kg/d, and increased plasma urea concentration in th ose receiving 2000 mg/kg/d. Moreover, increased plasma phospholipids and to tal cholesterol concentration, and increased liver and kidney weights were observed among treated animals. As a summary, the results have shown that irloxacin has a low acute toxicit y in both mice and rats. For repeat oral administration in rats, 100 mg/kg can be considered as the non-toxic effect level after a treatment period of 13 weeks.