摘要
目的研究连续静脉给予左旋泮托拉唑钠30 d对SD大鼠产生的全身毒性反应。方法 左旋泮托拉唑钠80、40、20 mg·kg-1·d-1(高、中、低剂量),泮托拉唑钠80 mg·kg-1·d-1连续静脉给药30 d,分别于末次给药后24 h和停药后14 d时取部分大鼠进行血液学指标、血液生化学指标、组织病理学检查。结果 左旋泮托拉唑钠高剂量组大鼠每次给药后即刻出现呼吸急促、步态不稳、俯卧不动等症状。与溶剂对照组比较,高剂量给药30 d后可导致大鼠血液中总胆固醇(TC)含量明显升高、Na+、Cl-水平明显降低(P<0.05);停药14 d后,各项指标均恢复正常。泮托拉唑钠组给药30 d同样可导致总胆固醇含量显著升高,Na+、Cl-水平明显降低;且可引起肝脏相对重量显著升高。停药恢复14 d后上述指标均恢复正常。结论 重复大剂量给予左旋泮托拉唑钠,可导致大鼠血液总胆固醇含量可逆性升高以及电解质水平可逆性改变,相同剂量下左旋泮托拉唑钠与泮托拉唑钠的毒性基本一致,但等效剂量下左旋泮托拉唑钠(40 mg·kg-1·d-1)的毒性明显低于泮托拉唑钠(80 mg·kg-1·d-1)。
Objective The systemic toxicities of S-（-）-pantoprazole sodium in rats following intravenous injuction for 30 d were studied. Methods One hundred rats were divided randomly into 5 groups： vehicle control group, pantoprazole sodium control group and three S-（-）-pantoprazole sodium groups with different dosages, and received vehicle, pantoprazole sodium（80 mg·kg-1·d-1）,S-（-）-pantoprazole sodium（80, 40 and 20 mg·kg-1·d-1） by i.v.via tail vein. Administrations were performed each day for consecutive 30 d. Haematological parameters, biochemical parameters, and histopathology analysis were determined at 30 d of treatments and 14 d after the withdrawal, respectively. Results The rats in the S-（-）-pantoprazole sodium group at 80 mg·kg-1·d-1 apperanced shortness of breath, unsteady gait, lying motionless and other symptoms. The levels of TC, Na＋, Cl- in this group were significantly higher or lower than those in vehicle control group at 30 d（P〈0.05）, The change of these parameters regained to normal at 14 d after withdrawal. Conclusion： Intravenous administration of the S-（-）-pantoprazole sodium for 30 d at high dose could induce reversible damage to liver and electrolyte. The toxicity of S-（-）-pantoprazole sodium is similar with pantoprazole sodium at the same dosage.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2013年第13期1060-1064,共5页
Chinese Pharmaceutical Journal
关键词
左旋泮托拉唑钠
泮托拉唑钠
全身毒性
大鼠
重复给药
尾静脉
S-（-）-pantoprazole sodium, pantoprazole sodium, systemic toxicity, rat, consecutive intravenous injection, caudal vein
作者简介
戴晓莉,女,主管药师 研究方向：新药毒理
通讯作者： 郭秀丽,女,教授 研究方向心血管药理学,肿瘤药理学,活性化药物筛选和药效学评价 Tel（0531）88382490 Email： guoxl@sdu.edu.cn
