注射用左旋泮托拉唑钠对家兔胚胎-胎仔发育的毒性  

Embryo-fetal development toxicity of S-(-)-Pantoprazole sodium for injection

作　　者：蔡鸣[1] 舒斌[1] 乔红群[2] 刘晶[1] CAI Ming;SHU Bin;QIAO Hongqun;LIU Jing(Jiangsu Provincial Institute of Materia Medica,Nanjing,Jiangsu,210009 P.R.China;Nanjing Tech University,Nanjing, Jiangsu,211816 P.R.China)

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,江苏南京211816

出　　处：《华西药学杂志》2019年第1期43-46,共4页West China Journal of Pharmaceutical Sciences

基　　金：江苏省政策引导类计划项目[产学研合作-前瞻性联合研究项目(BY2016005-10)]

摘　　要：目的考察静脉给予注射用左旋泮托拉唑钠对家兔胚胎-胎仔发育的影响。方法将孕兔随机分为正常组、阳性组(10 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))及注射用右旋泮托拉唑钠组(60 mg·kg^(-1)),在妊娠期(GD)6～18 d时静脉注射给药,于GD29处死家兔,记录各项指标。结果与空白组比较,左旋泮托拉唑钠组和右旋泮托拉唑钠组孕兔在孕期内的体质量增加量明显下降;泮托拉唑钠左、右旋体均未对妊娠结局产生明显影响,亦未对胎兔顶臀长、体质量、性别比产生明显影响;60 mg·kg^(-1)泮托拉唑钠左旋体和右旋体均可对胎兔的骨骼发育产生明显的不利影响。结论在试验条件下,静脉给予孕兔30 mg·kg^(-1)注射用左旋泮托拉唑钠未见明显胚胎-胎仔毒性,其对母体的无可见不良作用水平剂量为30 mg·kg^(-1)。OBJECTIVE To study the embryo -fetal development toxicity of S -(-)-Pantoprazole sodium for injection on pregnant rabbits.METHODS Pregnant rabbits were randomly divided into the normal group,positive group (10 mg.kg-1 Cyclophosphamide for injection),S -(-)-Pantoprazole sodium for injection(15,30,60 mg.kg-1)groups and R -(+)- Pantoprazole sodium for injection (60 mg.kg^-1)group.All the pregnant rabbits were intravenous injected the corresponding drugs from gestation day (GD)6 -18.Pregnat rabbits were sacrificed on GD 29,and various indications were recorded. RESULTS Compared to the normal group,net weight gain during pregnancy deelined significantly in the S -(-)- Pantoprazole sodium and R -(+)-Pantoprazole sodium groups.S -(-)-Pantoprazole sodium and R -(+)-Pantoprazole sodium had no significant effect on the perinatal outcome,and no remarkable influence on length and weight as well as sex ratio on fetal rabbits.Adverse effects were shown on skeleton development of fetal rabbits at the dosage of 60 mg ·kg^-1 CONCLUSION Under the experimental conditions,the S -(-)-Pantoprazole sodium for injection has no obvious embryo - fetus development toxicity on pregnant rabbits at the dose of 30 mg·kg^-1.The no observed adverse effect level (NOAEL)of S - (-)-Pantoprazole sodium for injection for matrix is 30 mg·kg^-1.

关 键 词：泮托拉唑钠 质子泵抑制剂 左旋体 右旋体 家兔 胚胎-胎仔发育毒性 手性药物 Me—too药物 环磷酰胺 安全性评价 生殖毒性 无可见不良作用剂量水平(NOAEL) 

分 类 号：R96[医药卫生—药理学]