本维莫德的单次给药和重复给药毒性研究  

Toxicity studies of benvitimod after single dose administration and repeated dose administration

作　　者：孙丽[1] 李健雄 刘全海[3] 刘珉宇[3] SUN Li;Li Jian-xiong;LIU Quan-hai;LIU Min-yu(Women's Hospital of Nanjing Medical University,Nanjing Maternity and Child Health Care Hospital,Nanjing 210004,China;Tianji Pharmaceutical Co.,Ltd.,Shenzhen 518052,China;Pharmacology Department of Shanghai Institute of Pharmaceutical Industry,Shanghai 200437,China)

机构地区：[1]南京医科大学附属妇产医院南京市妇幼保健院,南京210004 [2]天济药业(深圳)有限公司,深圳518052 [3]上海医药工业研究院药理室,200437

出　　处：《中国新药杂志》2023年第5期481-491,共11页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项资助项目(2009ZX09102-061)。

摘　　要：目的:观察皮下注射给予本维莫德的单次给药和重复给药毒性反应,为临床安全用药提供依据。方法:单次给药毒性研究通过皮下注射方式一次性给予受试动物本维莫德2000 mg·kg^(-1)(小鼠)或500 mg·kg^(-1)(家兔),给药后连续观察14~15 d,记录受试动物毒性反应及死亡情况。重复给药毒性研究通过皮下注射方式给予本维莫德40,100,200 mg·kg^(-1)·d^(-1)(大鼠)或30,60,150 mg·kg^(-1)·d^(-1)(家兔),连续注射6个月,给药结束后观察1个月。每日观察实验动物一般情况,每周测量实验动物体重及摄食量,末次给药终止后24 h,每组取50%受试动物(雌雄各半)进行血液生化学及病理学检查。剩余受试动物停药1个月,同前完成相应指标检查。结果:小鼠单次给药的无可见有害作用水平(no observed adverse effect level,NOAEL)剂量为2000 mg·kg^(-1),家兔单次给药的NOAEL剂量为500 mg·kg^(-1)。大鼠6个月重复给药的NOAEL剂量为200 mg·kg^(-1),家兔6个月重复给药的NOAEL剂量为150 mg·kg^(-1)。结论:本维莫德安全性良好。Objective:To observe the single dose toxicity and repeated dose toxicity of benvitimod,and to provide evidence for clinical administration and drug safety.Methods:Single dose toxicity:The animals were given benvitimod 2000 mg·kg^(-1)(mice)or 500 mg·kg^(-1)(rabbits)by subcutaneous injection.After administration,the animals were continuously observed for 14~15 days,and the toxic reaction and deaths were recorded.Repeated dose toxicity:benvitimod was administered subcutaneously to rats at doses of 40,100,and 200 mg·kg^(-1)·d^(-1)and to rabbits at doses of 30,60,150 mg·kg^(-1)·d^(-1)for 6 months and observed for 1 month after the end of administration.The general conditions of the experimental animals were observed daily,and the body weight and food intake of the experimental animals were measured weekly.Twenty-four hours after the last administration,50%of the animals(male and female)in each group were taken for hematology,blood biochemistry and pathology examination.The remaining animals were discontinued for 1 month,and the corresponding indexes were checked as before.Results:In the study of single dose toxicity,the NOAEL dose of benvitimod was 2000 mg·kg^(-1)on mice and 500 mg·kg^(-1)on rabbit.In the study of repeated dose toxicity,after 6 months of subcutaneous injection,the NOAEL dose of benvitimod was 200 mg·kg^(-1)on rats and 150 mg·kg^(-1)on rabbit.Conclusion:The results indicated that benvitimod had good safety in the clinical dosage.

关 键 词：本维莫德 单次给药毒性研究 重复给药毒性研究 临床前安全性评价 

分 类 号：R992[医药卫生—毒理学]