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中国临床药理学与治疗学 ›› 2003, Vol. 8 ›› Issue (4): 396-400.

• 研究原著 • 上一篇    下一篇

Beagle狗口服盐酸脂壬仲胺180天的安全性评价

王爱平, 孙辉业1, 刘宝兴1, 廖明阳1, 沈伽弟1, 孙永立1, 袁本利1, 余寿忠1, 瞿文生1, 王和枚1, 郑德琪1, 李培忠1   

  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;
    1军事医学科学院毒物药物研究所,北京 100850
  • 收稿日期:2003-03-13 修回日期:2003-03-26 出版日期:2003-08-26 发布日期:2020-11-19
  • 通讯作者: 王爱平,男,硕士,研究员,硕士生导师,研究方向:新药的药理学与毒理学评价。Tel:010-83169349  E-mail:wap531220@163.com

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

WANG Ai-Ping, SUN Huei-Ye1, lIOU Bao-Xing1, lIAO Ming-Yang1, SHEN Jia-Di1, SUN Yong-Li1, YUAN Ben-Li1, YU Shou-Zhong1, QU Wen-Sheng1, WANG He-Mei1, ZHENG De-Qi1, li Pei-Zhong1   

  1. New Drugs Safety Evaluation Center,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China;
    1Institute ofPharmacology&Toxicology,Academy ofMilitary Medical Sciences,Beijing 100850,China
  • Received:2003-03-13 Revised:2003-03-26 Online:2003-08-26 Published:2020-11-19

摘要: 目的 评价Beagle狗口服盐酸脂壬仲胺(aliphatic nonyl secondary amine hydrochloride,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0.5 mg·kg-13个剂量组,分别相当于人临床拟用剂量的56 、14 和3.5倍;相当于狗有效治疗剂量的64 、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40min开始出现,持续约8h,第2天完全恢复正常。2.0mg·kg-1组约26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

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

Abstract: 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 0.5mg·kg-1body weight/day for 6 days/week.The administrationlasted for 180 days.RESULTS: Dogs receiving ANSA at the dose of 8.0 mg·kg-1showed heterotropia,congestion of conjunctiva,light reflex bluntness,nictitating membrane closed incompletely,and insipidity.Some individuals appeared muscle shivering.All those symptoms emerged 40 minuteslater after administering and holded on 8 hours,disappeared on the next day.The same symptoms in the dose of 2.0 mg·kg-1group,but those were slighter.Those symptoms were not found in the dose of 0.5 mg·kg-1grouPand 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-1of ANSA is a safe dose for oral gavage in Beagle dogs.

Key words: pharmacology, aliphatic nonyl secondary amine hydrochloride, repeated dose toxicity, Beagle dogs, chrinic toxicity, safety evaluation

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