注射用左旋泮托拉唑钠对家兔胚胎-胎仔发育的毒性
|
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 onpregnant 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 correspondingdrugs 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 declined significantly in the S-(-)-Pantoprazole sodium and R-( +)-Pantoprazole sodium groups. S-(-)-Pantoprazole sodium and R-( +)-Pantoprazolesodium had no significant effect on the perinatal outcome,and no remarkable influence on length and weight as well as sex ratioon 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).
OBJECTIVE To study the embryo-fetal development toxicity of S-(-)-Pantoprazole sodium for injection onpregnant 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 correspondingdrugs 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 declined significantly in the S-(-)-Pantoprazole sodium and R-( +)-Pantoprazole sodium groups. S-(-)-Pantoprazole sodium and R-( +)-Pantoprazolesodium had no significant effect on the perinatal outcome,and no remarkable influence on length and weight as well as sex ratioon 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).
引文
[1]Kromer W.Similarities and difference in the properties of substituted benzimidazoles:A comparison between pantoprazole and related compounds[J].Digestion,1995,56(5):443-454.
[2]Fitton A,Wiseman L.Pantoprazole:A review of its pharmacological properties and therapeutic use in acid-related disorders[J].Drugs,1996,51:460-482.
[3]Richardson P1,Hawkey CJ,Stack WA.Proton pump inhibitors.Pharmacology and rationale for use in gastrointestinal disorders[J].Drugs,1998,56(3):307-335.
[4]Mullin JM,Gabello M,Murray LJ,et al.Proton pump inhibitors:Actions and reactions[J].Drug Discovery Today,2009,14:648-660.
[5]孙祖越,周莉.药物生殖与发育毒理学[M].上海:上海科学技术出版社,2015.
[6]周莉,孙祖越.实验用兔和大鼠常见畸形图谱[M].上海:上海科学技术出版社,2015.
[7]蔡鸣,舒斌,邵卿,等.氘代沃替西汀氢溴酸盐的胚胎-胎仔发育毒性及伴随毒动学研究[J].华西药学杂志,2018,33(6):594-598.
[8]岳鹏,沈姣,蔡鸣,等.赤苷脉通注射液对大鼠生育力和早期胚胎发育的毒性研究[J].华西药学杂志,2016,31(2):162-164.
[9]陈波,张贤君,刘玉清,等.风湿平胶囊的胚胎毒性及致畸性[J].华西药学杂志,2007,22(4):404-405.
[10]岳鹏,沈姣,乔红群,等.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[J].华西药学杂志,2017,32(6):599-602.
[11]张焕灵,黄健,张慧.泮托拉唑用于妊娠剧吐的疗效观察[J].实用诊疗,2014,4(11):13-14.
[12]谭玉娟,马玉奎,方超.左旋泮托拉唑钠对幽门结扎大鼠胃溃疡模型的治疗作用[J].中国比较医学杂志,2015,25(8):54-57,88.
[13]Mano N,Oda Y,Takakuwa S,et al.Plasma direct injection high-performance liquid chromatographic method for simultaneously determining E3810 enantiomers and their metabolites by using flavoprotein-conjugated column[J].J Pharm Sci,1996,85(9):903-907.
[14]Stenhof H,Blomqvist A,Lagerstrom PO.Determination of the enantiomers of omeprazole in blood plasma by normal-phase liquid chromatography and detection by atmospheric pressure ionization tandem mass spectrometry[J].J Chromatogr B,1999,734(2):191-194.
[15]Ariens EJ.Nonchiral,homochiral and composile chiral drugs trends[J].Pharmacol Sci,1993,14:68-72.
[16]袁伯俊,廖明阳,李波.药物毒理学实验方法与技术[M].北京:化学工业出版社,2007:300-321.
[17]A Wallace Hayes.Principles and methods of toxicology[M].Fifth Edition.Florida:CRC Press,2007:1689.
[2]Fitton A,Wiseman L.Pantoprazole:A review of its pharmacological properties and therapeutic use in acid-related disorders[J].Drugs,1996,51:460-482.
[3]Richardson P1,Hawkey CJ,Stack WA.Proton pump inhibitors.Pharmacology and rationale for use in gastrointestinal disorders[J].Drugs,1998,56(3):307-335.
[4]Mullin JM,Gabello M,Murray LJ,et al.Proton pump inhibitors:Actions and reactions[J].Drug Discovery Today,2009,14:648-660.
[5]孙祖越,周莉.药物生殖与发育毒理学[M].上海:上海科学技术出版社,2015.
[6]周莉,孙祖越.实验用兔和大鼠常见畸形图谱[M].上海:上海科学技术出版社,2015.
[7]蔡鸣,舒斌,邵卿,等.氘代沃替西汀氢溴酸盐的胚胎-胎仔发育毒性及伴随毒动学研究[J].华西药学杂志,2018,33(6):594-598.
[8]岳鹏,沈姣,蔡鸣,等.赤苷脉通注射液对大鼠生育力和早期胚胎发育的毒性研究[J].华西药学杂志,2016,31(2):162-164.
[9]陈波,张贤君,刘玉清,等.风湿平胶囊的胚胎毒性及致畸性[J].华西药学杂志,2007,22(4):404-405.
[10]岳鹏,沈姣,乔红群,等.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[J].华西药学杂志,2017,32(6):599-602.
[11]张焕灵,黄健,张慧.泮托拉唑用于妊娠剧吐的疗效观察[J].实用诊疗,2014,4(11):13-14.
[12]谭玉娟,马玉奎,方超.左旋泮托拉唑钠对幽门结扎大鼠胃溃疡模型的治疗作用[J].中国比较医学杂志,2015,25(8):54-57,88.
[13]Mano N,Oda Y,Takakuwa S,et al.Plasma direct injection high-performance liquid chromatographic method for simultaneously determining E3810 enantiomers and their metabolites by using flavoprotein-conjugated column[J].J Pharm Sci,1996,85(9):903-907.
[14]Stenhof H,Blomqvist A,Lagerstrom PO.Determination of the enantiomers of omeprazole in blood plasma by normal-phase liquid chromatography and detection by atmospheric pressure ionization tandem mass spectrometry[J].J Chromatogr B,1999,734(2):191-194.
[15]Ariens EJ.Nonchiral,homochiral and composile chiral drugs trends[J].Pharmacol Sci,1993,14:68-72.
[16]袁伯俊,廖明阳,李波.药物毒理学实验方法与技术[M].北京:化学工业出版社,2007:300-321.
[17]A Wallace Hayes.Principles and methods of toxicology[M].Fifth Edition.Florida:CRC Press,2007:1689.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |