注射用左旋泮托拉唑钠对大鼠胚胎-胎仔发育的毒性及伴随毒代动力学研究  

Study on the embryo-fetal development toxicity and toxicokinetics of( S )-(-)-Pantoprazole sodium for injection in rats

作　　者：岳鹏[1] 沈姣[1] 乔红群[2] 张梣 刘晶[1] 

机构地区：[1]江苏省药物研究所,江苏南京210009 [2]南京工业大学药学院,江苏南京211816

出　　处：《华西药学杂志》2017年第6期599-602,共4页West China Journal of Pharmaceutical Sciences

基　　金：江苏省政策引导类计划(产学研合作)--前瞻性联合研究项目(BY2015005-04)

摘　　要：目的考察给予静脉注射用左旋泮托拉唑钠对大鼠胚胎-胎仔发育毒性的影响。方法将孕鼠随机分为溶剂对照组、阳性对照组(2.8 mg·kg^(-1)注射用环磷酰胺)和注射用左旋泮托拉唑钠低、中、高剂量组(15、30、60 mg·kg^(-1)),在妊娠GD6-15时静脉注射给药,GD20时处死大鼠,记录各项指标,并检测左旋泮托拉唑钠在孕鼠和仔鼠体内的组织分布。结果左旋泮托拉唑钠可透过孕鼠的血脑屏障和胎盘屏障,透过量与给药剂量呈正相关,但左旋泮托拉唑钠各剂量组大鼠的指标与溶剂对照组的比较,无显著性差异。结论在试验条件下,注射用左旋泮托拉唑钠对孕鼠母体和胎鼠的生长发育无明显毒性作用,其安全剂量应≤60 mg·kg^(-1)。OBJECTIVE To investigate the embryo -fetus development toxicity of （S） - （ - ） -Pantoprazole sodium for injection on SD rats. METHODS The pregnant rats were randomly divided into the solvent control group, positive control group（2.8 mg.kg-1 cyclophosphamide） and（S） - （ - ） - Pantoprazole sodium for injection groups（ 15, 30 and 60 mg.kg-1 ） by iv during the gestation of 6- 15 days（ GD6- 15 ）. At termination （GD20）, pregnant rats were sacrificed and evaluated by the corpora lutea count, implantation sites, existence and death of embryos. Fetal sex ratio, weight, externals, variations and malformations of viscus and skeleton were observed. The distribution of （S） - （ - ） - Pantoprazole in pregnant rats and fetal rats were determined. RESULTS （S） - （ - ） - Pantoprazole could pass through placental - barrier and blood - brain barrier, and there was a positive correlation between the volume and the dosage of the pregnant rats. There was no significant difference in the indexes between three （S） - （ - ） - Pantoprazole groups and the solvent control group. CONCLUSION Under the experimental conditions, the （S） - （ - ） - Pantoprazole sodium for injection has no obvious embryo -fetus development toxicity on SD rats when the dose was below 60 mg·kg-1.

关 键 词：左旋泮托拉唑钠 大鼠 胚胎-胎仔发育毒性 安全性评价 伴随毒代动力学 胎盘屏障 致畸敏感期 生殖毒性 

分 类 号：R96[医药卫生—药理学]