加替沙星犬静脉给药的长期毒性研究

Veinal Toxicity Study of Gatifloxacin in Beagle Dogs

观察了加替沙星连续静脉注射 (iv)给药 13周对Beagle犬所发生的各种反应 ,评价加替沙星的安全性。加替沙星以 0 ,8,16 ,32mg/kg每天给药一次 ,每周 6天。结果表明 ,iv加替沙星后 ,犬出现恶心、呕吐、排便、皮肤潮红、眼睑红肿、流涎、活动减少等现象。所有症状在给药后 2h均可恢复。动物可见食欲不振 ,第 3周恢复正常。对犬的血常规、血清生化、血清离子、尿、粪常规、体重增长、心电图等均未发现明显的异常变化。组织切片检查表明 ,在所有受检脏器中 ,高剂量组 1例 (1/2 )标本出现轻度肝细胞脂肪变性 ,但在恢复期该病变可以恢复。其余脏器均未见明显的病理改变。在本试验条件下 ,iv加替沙星给药 13周对犬的无毒剂量为 16mg/kg。

The 13-week repeated veinal dose toxicity study of gatifloxacin was conducted in Beagle dogs at once-daily doses of 0, 8, 16, 32 mg/kg. No deaths occurred in any group. As main clinical signs or changes due to the drug treatment, decreased appetite, nausea, vomiting, defecating, dermal rubeosis, eyelid flare, salivating, reduced locomotor activity were noted only in the 32 mg/kg dose group, but rapidly disappeared. There were no drug-related changes in food intake, urinalysis, fecal occult blood test, body weight, electrocardiogram, hematology, blood chemistry, hepatic and renal function tests, organ weight and autopsy except the slightly fatty degeneration of hepatocyte. From these results, the non-toxic dose of gatifloxacin was estimated to be 16 mg/kg under the present study conditions.