title: Acute and subchronic toxicity studies of the new quinolone antibacterial agent irloxacin in rodents.
abstract: 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 intraperitoneal route in oder to study its acute toxicity. Its oral subchronic toxicity was also assessed by treating rats for 4 and 13 weeks. The results obtained showed that irloxacin was well tolerated after single administration in mice and rats, with LD50 values above 2000 and 5000 mg/kg for intraperitoneal and oral administration, respectively. In the oral subchronic toxicity studies, the histopathological examination performed after the 13-week treatment period confirmed the kidney as the target organ for toxicity. Increased 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 tubules and chronic interstitial nephritis in males receiving these dosages. No histopathological findings were observed in the kidneys of animals receiving 100 mg/kg/d for 13 weeks. Other relevant findings were, presence of dark or cloudy urine with slightly lower pH in animals receiving dosages of 450 mg/kg/d and above, increased urinary protein concentration in animals receiving 2000 or 450 mg/kg/d, and increased plasma urea concentration in those receiving 2000 mg/kg/d. Moreover, increased plasma phospholipids and total 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 toxicity 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.
authors.affiliation: Toxicology Department, Laboratorios Dr. Esteve S.A., Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Guzmán
authors.forename: C
authors.initials: C
authors.lastname: García
authors.forename: I
authors.initials: I
authors.lastname: Demestre
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000097:blood; D005260:Female; D024841:Fluoroquinolones; D007274:Injections, Intraperitoneal; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D004798:Enzymes; D024841:Fluoroquinolones; C046067:pirfloxacin; D002939:Ciprofloxacin