复方萘酚喹对比格犬的长期毒性  

Long-term toxicity of co-naphthoquine in beagle dogs

作　　者：王京燕[1] 邬伯安[1] 徐在海[1] 孙国章[1] 张敏[1] 王翠娥[1] 刘超[1] 吕富双[1] 孙志伟[1] 洪松芳[1] 乌增炎[1] 叶洪金[1] 

机构地区：[1]军事医学科学院微生物流行病研究所,北京100071

出　　处：《军事医学科学院院刊》2003年第3期196-198,226,共4页Bulletin of the Academy of Military Medical Sciences

基　　金：总后指令性课题 ( 96L0 2 3 )

摘　　要：目的 :观察犬连续口服复方萘酚喹的毒性剂量、损伤的靶器官、可逆性及安全剂量范围。方法 :给比格犬口服复方萘酚喹 1 7.5 ,87.5或 1 4 0mg/(kg·d) ,每天 1次 ,连服 1 4d。给药结束后 ,各组活杀 2 /3,留 1 /3继续观察2 8d。观测了临床症状和生理指标 ,血液学 8项、血生化 1 3项、尿 8项、心电图、眼底、骨髓和组织病理学。结果 :主要毒性反应见于 1 4 0mg/(kg·d)组 ,给药后 5 /6只犬出现恶心、呕吐等消化系统症状 ,部分动物出现阵发性抽搐 ,几分钟后自行缓解。该组给药后GOT ,GPT明显升高 ,心电图Q_T间期延长 ,骨髓红系受到抑制 ,组织学检查可见肝细胞损伤明显。 87.5mg/(kg·d)组各种毒性反应均较大剂量组轻 ,所有毒性反应于停药后自行恢复。 1 7.5mg/(kg·d)组未见明显毒副作用。结论 :1 4 0mg/(kg·d)为重度中毒剂量 ,87.5mg/(kg·d)为中度中毒剂量 ,1 7.5mg/(kg·d)为安全剂量。毒性靶器官是肝脏和骨髓 。Objective:To observe the toxic reactions of beagle dogs caused by continuous po administration of the co_naphthoquine, including the toxic dose, the target organs, the safety range and the recovery after drug withdrawal.Methods:The dogs were randomly divided into three dose groups [17.5,87.5,140?mg/(kg·d)] and a blank control group. Each group consisted of 3 males and 3 females. The drug was given once a day for 14 successive days. Manifestations and behaviors of the dogs, hematology, blood chemistry, urinalysis, electrocardiogram, eyeground, necropsy, bone marrow and histopathology were examined. Twenty_four hours after the last dose, 4 dogs of each group were sacrificed and the remaining 2 dogs in each group were further observed for four weeks.Results:The results revealed that 140?mg/(kg·d) had serious toxicity. The main toxic manifestations of the dog were nausea and vomiting. Some animals demonstrated paroxysmal twitch, which stopped spontaneously without any treatment. After administration, extended Q_T interval , increase in GOT and GPT, erythropoietic suppression of the bone marrow, degenerative changes in the parenchymal cells of liver were observed. All of these changes were less serious in 87.5?mg/(kg·d)group than those in 140?mg/(kg·d)group. Conclusions:The dose of 140?mg/(kg·d) was toxic, 87.5?mg/(kg·d) had mild toxicity and 17.5?mg/(kg·d) was safe. The liver and bone marrow could be assumed as the most sensitive target organs. All of the changes were reversible after stopping treatment.

关 键 词：抗疟药 复方萘酚喹 萘酚喹 青蒿素 毒性 狗 

分 类 号：R96[医药卫生—药理学]