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

被引:0
|
作者
Guzmán, A [1 ]
García, C [1 ]
Demestre, I [1 ]
机构
[1] Lab Dr Esteve SA, Dept Toxicol, Barcelona 08041, Spain
来源
ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH | 2000年 / 50卷 / 05期
关键词
antibacterials; CAS; 91524-15-1; irloxacin; dog; toxicity studies; quinolones;
D O I
暂无
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The subchronic oral toxicity of the new quinolone antibacterial agent irloxacin (6-fluorine-7-(pyrrol-1-yl)-l-ethyl-l,4-dihydro-4-oxo-quinolone-3-carboxylic 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 receiving 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 one female experienced transitory locomotive difficulties at the end of the first week of treatment. The liver was identified as the target organ for toxicity 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 observed in animals receiving 120 or 1400 mg/kg/d for 4 weeks, and in all groups receiving irloxacin for 29 weeks. However, no histopathological findings 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 cholesterol levels in males receiving 120 mg/kg/d and animals receiving 1400 mg/kg/d, increased albumin and decreased betaglobulin concentrations in females receiving 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.
引用
收藏
页码:485 / 494
页数:18
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