1,6-二磷酸果糖钙盐狗急性毒性和长期毒性研究  

Study on acute and long-term toxicity of FDP-Ca_2 on dogs

作　　者：唐萌[1] 应汉杰[2] 谈伟君[1] 王习霞 张文举 欧阳平凯[2] 李纯德[1] 滕蔓 虞秀珍 

机构地区：[1]东南大学公共卫生学院,江苏南京210009 [2]南京工业大学,江苏南京210009

出　　处：《东南大学学报（医学版）》2002年第1期109-114,共6页Journal of Southeast University(Medical Science Edition)

基　　金：国家"八五"攻关项目(85 08 03 11)

摘　　要：目的 :探讨 1,6 二磷酸果糖钙盐 (FDP Ca2 )单次或多次给药后动物出现的毒性反应及其性质和程度 ,寻找主要的靶器官、无毒反应剂量及药物的安全范围 ,以推断人的临床用量。方法 :按照新药临床前安全性评价的要求进行狗急性毒性和长期毒性研究。结果 :狗经口急性毒性试验各剂量组未见明显中毒症状 ,各剂量组化验检查指标也未见明显异常 ;长期毒性试验以 15 0 0mg·kg-1给药 12周 ,狗的血肌酐值与对照组比较差异有显著性 (P <0 .0 5 ) ,其它未见明显异常 ,恢复期后实验组与对照组各项指标比较差异均无显著性 (P >0 .0 5 )。结论 :FDP Ca2 临床治疗量为 2 5～ 5 0mg·kg-1·d 1,仅为狗急性毒性试验安全量的1/2 0 0 ,5 0 0mg·kg-1为FDP Ca2 狗长期毒性试验的无毒反应剂量 ,此剂量为临床实际用量的10～ 2 0倍 ,因而推断FDP Ca2 在临床长期口服 (治疗量为 2 5～ 5 0mg·kg-1·d 1)是安全的。Objective The purpose of the experiment was to probe into the animal's toxicity reaction,its nature and degree after receiving calcium fructose-1,6-diphosphate(FDP?Ca 2) once or repeatedly,look for the main target organ,nonpoisonous response dosage and safety range of the drug,and infer a clinical safety dosage.Methods The experiment was conducted according to the preclinical safety evaluation for new drugs.Results No obvious signs of toxicity and abnormality of laboratory parameters were found in all tested groups for acute toxicity experiment per os .In the long term toxicity experiment,the creatinine levels were significantly higher in 1?500?mg·kg -1 group at week 12,than those of control group( P <0.05).No significant difference in regard to the indexes studied was found between the experimental and control groups after recovery.Conclusions At present,the treatment dosage of FDP?Ca 2 is 25～50?mg·kg -1 ·d -1 body weight,which amounts to 1/200 of the safety dosage in acute toxicity,and nonpoisonous response dosage for long term toxicity experiment.We may ,therefore,reasona^bly conclude that it is safe to take FDP?Ca 2 orally over a long period of time at the dose of 25～50?mg·kg -1 ·d -1 .

关 键 词：1 6-二磷酸果糖钙盐 急性毒性 长期毒性 安全性评价 狗 

分 类 号：R99[医药卫生—毒理学]