左旋泮托拉唑钠临床前毒理学研究  

Preclinical Toxicologic Studies of (L-)pantoprazole Sodium

作　　者：郭锋[1] 陆华龙 陈根[1] 刘彦梅[1] 唐江琼[1] 秦旭平[1] 

机构地区：[1]南华大学药物药理研究所,湖南衡阳421001 [2]扬州天创医药科技有限公司

出　　处：《中南医学科学杂志》2012年第1期51-54,共4页Medical Science Journal of Central South China

摘　　要：目的通过研究左旋泮托拉唑钠在动物的毒性反应,为后续临床研究提供剂量设置依据。方法以小鼠、大鼠、Beagle犬为试验对象,观察左旋泮托拉唑钠在三种动物的急慢性毒性反应。检测其红细胞(RBC)、白细胞(WBC)、血红蛋白(HGB)等血液学和谷-丙转氨酶(ALT)、谷-草转氨酶(AST)、胆固醇(CHOL)等生化学指标,肉眼观察并测量主要靶器官(心、肺、肾、肝)变化。结果左旋泮托拉唑钠小鼠的半数致死量(LD50)为381.52 mg/kg。犬在剂量为150 mg/kg时,急性毒性主要表现为震颤、唾液分泌增加、瘫软及呕吐,然后20 min后死亡。在长期毒性试验,给大鼠左旋泮托拉唑钠低、中、高(10、30、90 mg/kg)剂量组,给药31天时,高剂量组大鼠血清ALT、AST及CHOL均有一定程度升高,且大鼠摄食量和体重均有一定下降。结论左旋泮托拉唑钠小鼠的LD50为381.52 mg/kg,Beagle犬在67 mg/kg时即出现一定程度的毒性反应。急性毒性反应与神经系统有关,未见脏器有明显损伤。在长期使用高剂量左旋泮托拉唑钠(90 mg/kg)可引起大鼠WBC、RBC降低,血清中AST、ALT、CHOL升高。Objective To explore the toxical action of（L-） pantoprazole sodium in the animals and to provide the dose to clinical research.Method Take mice,rats and Beagle dogs as the research objects,and observe the toxical reaction of（L-） pantoprazole sodium in the animals above.Hematology such as red blood cell（RBC）,white blood cell（WBC） and blood biochemical parameters were analyzed.The important target organs（heart,kidney,brain and liver） were observed and measured by eye.Results The lethal dose（LD） of（L-） pantoprazole sodium for mice was 381.52mg/kg.When the Beagle dogs were injected with（L-） pantoprazole sodium in the dose of 150 mg / kg,the acute toxic reactions were body shaking,excessive flow of saliva,paralyzed,and vomiting,then died in 20 min later.The chronic toxic reaction of（L-） pantoprazole sodium at high,medium,and low doses（10,30,and 90 mg / kg） by iv gtt for 31 days in the rats,and the ALT,AST were raised,their quantity of food and body weight were decreased.Conclusion The lethal dose（LD） of（L-） pantoprazole sodium for mice was 381.52mg/kg.At the dose of 67 mg/kg,the Beagles showed a degree of toxic reaction,the acute reaction of the chemical was related to nervous system,and no organ was obviously hurt.（L-） pantoprazole sodium（90 mg/kg）can decrease the WBC and RBC,increase plasma AST,ALT,CHOL in rats when it is used in long term.

关 键 词：左旋泮托拉唑钠 泮托拉唑钠 急性毒性 长期毒性 

分 类 号：R994.1[医药卫生—毒理学]