注射用克拉霉素对Beagle犬4周重复给药毒性实验研究

目的研究连续静脉注射给予注射用克拉霉素对Beagle犬的毒性作用。方法以正常Beagle犬为研究对象，连续静脉注射给药4周，以其体重、血液生化学、血液学、脏器相对重量、组织病理学检查为指标，全面评价其对Beagle犬的毒性作用。结果注射用克拉霉素80mg·kg^-1剂量可引起Beagle犬肝功能（AST、ALT）和肾功能（BuN）指标异常，组织病理学检查可见肝细胞呈条索状排列，窦周隙增宽，部分肝细胞变性、坏死或出现核固缩以及肾脏毛细血管扩张充血，部分肾小管上皮细胞变性、坏死或发生固缩，停药2周后上述异常指标及病理学改变恢复正常。结论大剂量注射用克拉霉素重复给药可影响Beagle犬肝肾功能，导致可逆性的肝、肾生化指标异常及病理改变。

Four Weeks Intravenous Repeated Dose Toxicity of Clarithromycin for Injection in Beagle Dogs

Objective To investigate the repeated dose toxicity of clarithromycin for injection in dogs. Methods The normal dogs were administered with clarithromycin for injection by intravenous injection for four weeks. The body weight,blood biochemistry, hematology, viscera relative weight and histopathology were measured for the overall toxicity assessment. Results The normal dogs administered with clarithromycin for injection（80mg· kg^-1） showed abnormal escalation of the levels of aspartic transaminase（AST）, alanine aminotransferase（ALT）, urea nitrogen（BUN）. Histopathological examination indicated that the liver cells were cord-like arranged and perisinusoidal space was broadened,some liver cells degenerated, necrosed or appeared karyopyknosis. Renal capillary dilatation and congestion, epithelial cell degeneration, necrosis or pyknosis of partial renal tubular were also found by histopathological examination. Conclusion Repeated administration of clarithromycin at high dose could lead to abnormal biochemical index and pathological lesions of liver and kidney in dogs.