溴莫普林家犬13周亚急性毒性研究

Thirteen week repeateddose toxicity of antibiotic brodimoprim in dogs

观察杂种犬溴莫普林经口给药１３周的毒性反应，以评估其用药安全性。试药剂量为４０、２０、１０．０及０ｍｇ／（ｋｇｄ），按新药临床前毒理研究规范进行，并增加了骨髓涂片的细胞学检查及血清Ｎａ＋、Ｋ＋、Ｃｌ－离子检测。结果主要毒副反应有呕吐，腹泻，红细胞计数及血红蛋白下降，网织红细胞增多，ＡＬＴ、ＡＳＴ、Ｃｒｅａ升高，肝脏及肾脏出现细胞变性坏死、炎症细胞浸润，骨髓细胞增生活跃，幼红细胞增多，粒红比值下降。在４周停药期可基本恢复，无延迟性毒性反应。结论：溴莫普林犬１３周给药的无毒剂量为１０ｍｇ／（ｋｇｄ），中毒剂量为４０ｍｇ／（ｋｇｄ），毒性靶器官为肝、肾、血液及骨髓的红细胞系统。

Thirteen week oral subacute toxicity of antibiotic brodimoprim, a new DIPP antibiotic, was investigated in dogs of both sexes. The animals were treated with the antibiotic at dose level of 40, 20, 10 and 0 mg/(kgd). No change was observed in the 10 mg/(kgd) group. Vomit, diarrhoea were seen in the 20 or 40 mg/(kgd) group. There were increases of ALT, AST and Crea, and decreases of RBC and Hb. The main histopathology changes were degeneration and necrosis of the hepatocytes and renal tubular epithelium, inflammation cell infiltrate in the liver and kidney. There were increases of erythroblast, and decreases of granulocyte ratio to erythrocyte in bone marrow in dogs of 40 mg/(kgd) group. These changes were recoverable after withdrawal. According to the results of the study, the safety dose was considered to be 10 mg/(kgd). The targt organs of toxicity were liver, kidney, blood and hemopoietic system.