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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。
OBJECTIVE: To evaluate the toxic effects of oral administration of 6-MON of oral pamidoneylsecondaryamine hydrochloride (ANSA) in beagle dogs, provide target organs for toxic reactions and their reversibility, and determine the dose of non-toxic reaction. Methods: ANSA 8.0,2. 0 and 0 .5mg · kg-13 dose groups, which were respectively equivalent to 5, 6, 14 and 3.5 times of the human clinical trial dose; 16 and 4 times. Another set of blank control group. Beagle dogs in each group 6, male and female. Weekly dosing 6d, oral 1 times a day for 180 days. Results: The animals in 8.0mg · kg-1 group had strabismus above the corner of the eye outward after administration. The conjunctival hyperemia at the lower part of the conjunctiva showed a half-closed state. The pupillary light reflex was pure, and the patient was in a sluggish state. In severe cases, muscle shiver occurred. These symptoms began to appear about 40min after the drug, lasted about 8h, the first 2 days completely returned to normal. About 2 6 animals in the 2.0 mg · kg -1 group showed the same symptoms but had less symptoms. No abnormalities were observed in the 0.5 mg · kg -1 group and the control group, and no direct organ injury was observed in the pathological examination after the Beagle dog was given the test sample. Each group of 13 hematology and 17 blood biochemical indicators were within the normal range. Conclusion: Under this test condition, the non-toxic reaction dose of alias-alminamide hydrochloride is 0.5 mg · kg-1.