Beagle狗口服盐酸脂壬仲胺180天的安全性评价  

Toxicity of aliphatic nonyl secondary amine hydrochloride administed orally for 180 days in Beagle dogs

作　　者：王爱平[1] 孙辉业[2] 刘宝兴[2] 廖明阳[2] 沈伽弟[2] 孙永立[2] 袁本利[2] 余寿忠[2] 瞿文生[2] 王和枚[2] 郑德琪[2] 李培忠[2] 

机构地区：[1]中国医学科学院中国协和医科大学新药安全评价研究中心,北京100050 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中国临床药理学与治疗学》2003年第4期396-400,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的 :评价Beagle狗口服盐酸脂壬仲胺 (ali phaticnonylsecondaryaminehydrochloride ,ANSA ) 6mon产生的毒性作用 ,提供毒性反应的靶器官及其损害的可逆性 ,确定无毒反应剂量。方法 :本试验设ANSA 8.0、2 .0和 0 .5mg·kg-13个剂量组 ,分别相当于人临床拟用剂量的 5 6、14和 3.5倍 ;相当于狗有效治疗剂量的 6 4、16和 4倍。另设空白对照组。每组Beagle犬 6只 ,雌雄各半。每周给药 6d ,每天口服 1次 ,连续 180d。结果 :8.0mg·kg-1组动物先后于给药后出现眼球向外眼角上方斜视 ,结膜下部充血 ,瞬膜呈半闭合状态 ,瞳孔对光反射迟纯 ,精神不振 ,严重者出现肌肉颤抖。这些症状约在药后4 0min开始出现 ,持续约 8h ,第 2天完全恢复正常。2 .0mg·kg-1组约 2 6动物出现同样症状 ,但症状较轻。 0 .5mg·kg-1组和对照组动物未见异常 ,病理组织学检查未见Beagle狗给予供试品后造成的直接脏器损伤。各组 13项血液学和 17项血液生化学指标均在正常范围之内。结论 :在本次试验条件下 ,盐酸脂壬仲胺的无毒反应剂量为 0 .5mg·kg-1。AIM: To evaluate the toxicity of aliphatic nonyl secondary amine hydrochloride administed orally for 180 days in Beagle dogs. METHODS: 24 Beagle dogs were divided into four groups, each consisting of 3 males and 3 females, administered ANSA once daily by oral gavage at doses of 0 (control), 8.0 , 2.0 , and 0.5 mg·kg -1 body weight/day for 6 days/week. The administration lasted for 180 days. RESULTS: Dogs receiving ANSA at the dose of 8.0 mg·kg -1 showed heterotropia, congestion of conjunctiva, light reflex bluntness, nictitating membrane closed incompletely, and insipidity. Some individuals appeared muscle shivering. All those symptoms emerged 40 minutes later after administering and holded on 8 hours, disappeared on the next day. The same symptoms in the dose of 2.0 mg·kg -1 group, but those were slighter. Those symptoms were not found in the dose of 0.5 mg·kg -1 group and control group. Histopathological examination did not shown any direct injury from the treatment. No abnormity was detected from haematology and serum biochemistry analysis. CONCLUSION: The 0.5 mg·kg -1 of ANSA is a safe dose for oral gavage in Beagle dogs.

关 键 词：药理学 盐酸脂壬仲胺 重复给药毒性 Beagle狗 长期毒性 安全评价 

分 类 号：R965.3[医药卫生—药理学] R972.4[医药卫生—药学]