中国药物警戒 ›› 2017, Vol. 14 ›› Issue (8): 453-456.

• 基础与临床研究 • 上一篇    下一篇

注射用右旋雷贝拉唑钠Beagle犬13周重复给药毒性实验研究

刘翠玲1, 戴晓莉2, 马玉奎*, 孙蓉3,   

  1. 1.山东省临朐县人民医院，山东 临朐，262600；
    2. 山东省药学科学院，山东 济南 250100；3. 山东省中医药研究院，山东 济南 250014
  • 收稿日期:2017-05-11 修回日期:2017-09-26 出版日期:2017-08-20 发布日期:2017-09-26
  • 通讯作者: 马玉奎，男，博士，主任药师，新药安全性评价。 E-mail：yukuima@sina.com
  • 作者简介:刘翠玲，女，本科，主管药师，药物不良反应检测。
  • 基金资助:
    山东省自主创新及成果转化专项（2014ZZCX02104）：药物安全性评价关键技术研究。

13 Weeks Intravenous Repeated Dose Toxicity Study of Dexrabeprazole Sodium for Injection in Beagle Dogs

LIU Cui-ling1, DAI Xiao-li2, MA Yu-kui2, SUN Rong3   

  1. 1.People's Hospital of Linqu County, Linqu 262600, China;
    2. Shandong Academy of Pharmaceutical Sciences, Jinan 250100, China;
    3. Shandong Academy of Chinese Medicine, Jinan 250014, China
  • Received:2017-05-11 Revised:2017-09-26 Online:2017-08-20 Published:2017-09-26

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摘要： 目的 研究重复静脉给予注射用右旋雷贝拉唑钠13周对Beagle犬产生的毒性，并与注射用雷贝拉唑钠进行比较。方法 正常Beagle犬50只，分为注射用右旋雷贝拉唑钠2.5、10、40 mg·kg-1 3个剂量组、注射用雷贝拉唑钠40 mg·kg-1对照组和溶剂对照组，每组静脉滴注给予相应剂量的药物溶液，每天1次，连续13周，停药恢复4周。每周称量1次体重，给药前、给药结束及恢复期结束进行体温、心电、眼科、尿液和粪便检查；采血进行血液学、血液生化学指标检测；给药结束及恢复期结束剖检进行脏器相对重量和组织病理学检查。结果 注射用右旋雷贝拉唑钠40 mg·kg-1剂量下可引起部分动物给药后即刻发现自主活动减少、呼吸急促、流涎、俯卧等症状，血液学指标RBC、HGB、HCT降低，血清生化学指标TP、ALB降低、TC、TG、BUN升高，肝脏相对重量增加以及甲状腺病理组织学病变。结论 重复静脉给予注射用右旋雷贝拉唑钠的主要毒性靶器官为肝脏、肾脏和甲状腺，相同剂量下毒性与注射用雷贝拉唑钠基本一致；犬最大无毒反应剂量（NOAEL）为2.5 mg·kg-1。

关键词: 注射用右旋雷贝拉唑钠, 重复给药毒性, 甲状腺, Beagle犬

Abstract: Objective To reach the repeated dose toxicity of dexrabeprazole sodium for injection in Beagle dogs and compare the toxicity with rabeprazole sodium for injection. Methods Fifty normal Beagle dogs were divided into five groups： solvent control group, rabeprazole sodium for injection group (40 mg·kg-1) and dexrabeprazole sodium injection group (2.5, 10 and 40 mg·kg-1). The dogs were administered intravenously with corresponding drug for 13 weeks continuously. The body weights were detected every week and body temperature, ECG, ophthalmology, urine and stool were examined before and after administration period and recovery for 4 weeks. The serum and plasma of dogs were collected to detect hematology and blood biochemistry index, and dogs were autopsied to detect viscera index and histopathology at the end of administration and recovery for 4 weeks. Results The main toxicity symptoms of some dogs administered with dexrabeprazole sodium for injection (40mg·kg-1) are decreased voluntary activity, shortness of breath, salivation and prone. Abnormal reduction of the levels of RBC, HGB, HCT, TP, ALB and escalation of the levels of TC, TG, BUN and kidney index were found after administration for 13 wk. Pathological changes of thyroid was also found by histopathological examination. Conclusion Major toxic target organs of Beagle dogs after administration with dexrabeprazole sodium for injection (40mg·kg-1) for 13 wk are liver, kidney and thyroid. The toxicity level is similar in dexrabeprazole sodium for injection group and rabeprazole sodium for injection group with same dose. No observed adverse effect level (NOAEL) in Beagle dogs is 2.5 mg·kg-1.

Key words: dexrabeprazole sodium for injection, repeated dose toxicity, thyroid, Beagle dog

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