头孢呋辛/他唑巴坦注射剂的毒理学研究

Toxicological studies of cefuroxime sodium and tazobactam sodium injection

目的分析头孢呋辛/他唑巴坦注射剂对小鼠的急性毒理学和大鼠的长期毒理学实验,为指导临床抗菌药物的合理应用提供参考依据。方法对60只小鼠及120只大鼠进行急性毒性实验及长期毒性实验,急性毒性实验选取禁食24h的60只的小鼠,每20只分别尾静脉注射头孢呋辛、他唑巴坦和头孢呋辛/他唑巴坦(4∶1)3种抗菌药物,连续注射1周;长期毒性试验选取120只大鼠,每20只分别腹腔注射头孢呋辛、他唑巴坦和头孢呋辛/他唑巴坦(4∶1)高2.4g/(kg·d)、中1.2g/(kg·d)、低0.6g/(kg·d)3个剂量,连续注射4周,注射后立刻观察动物的毒性反应,记录中毒情况;观察大鼠的各种临床表现、血液指标和解剖后的脏腑变化。结果急性毒性实验结果显示,头孢呋辛、他唑巴坦和头孢呋辛/他唑巴坦(4∶1)3种抗菌药物注射后,均无明显毒性异常表现发生;长期毒性实验结果显示,头孢呋辛/他唑巴坦(4∶1)高中低剂量组大鼠给药期间并无明显的异常表现;给药4周后,除高剂量组的红细胞和白细胞总数偏高之外,其他各项指标和单剂量相比差异无统计学意义;病理组织学检查和单剂量相比,差异无统计学意义。结论头孢呋辛/他唑巴坦(4∶1)与两者单剂量应用其急性毒性和长期毒性差异不大,且两者作为复方制剂联合应用,可以降低细菌的耐药性,在临床上对细菌的感染治疗值得推广。

OBJECTIVE To investigate cefuroxime sodium and tazobactam sodium injection in mice with acute toxicity test and rats with long-term toxicity test,so as to provide references for guiding clinical rational use of antibacterial agents.METHODS Totally 60 mice and 120 rats were conducted acute toxicity test and long-term toxicity test respectively.The acute toxicity test selected 60 mice that were fasted for 24 hours.And every 20 mice were intravenously injected with cefuroxime sodium,tazobactam sodium and mixed cefuroxime sodium/tazobactam sodium（4∶1）for a week;the long-term toxicity test selected 120 rats.Every 20 rats were intraperitoneally injected with cefuroxime sodium,tazobactam sodium and mixed cefuroxime sodium/tazobactam sodium（4∶1）with three levels of dose：2.4g/（kg·d）（high）,1.2g/（kg·d）（middle）and 0.6g/（kg·d）（low）for 4weeks.The toxic reactions were observed immediately after the injections.A variety of clinical manifestations,blood parameters and changes of organs after anatomy in rats were observed.RESULTS The acute toxicity test results showed that no abnormal manifestations occurred in mice injected with cefuroxime sodium,tazobactam sodium and mixed cefuroxime sodium/tazobactam sodium（4∶1）;long-term toxicity test results showed no remarkable abnormal behavior were found in rats infected with three levels of dose（high,middle and low）of mixed cefuroxime sodium/tazobactam sodium（4∶1）;after four weeks of administration,other than high-dose group was high in the number of erythrocytes and leukocytes,there are no significant differences compared in other indicators and single dose;the differences between histopathologic examination and single dose had no significance.CONCLUSIONThe mixed cefuroxime sodium/tazobactam sodium（4∶1）and both single-dose has few differences in treating acute toxicity and long-term toxicity,and combination of them as a compound preparation can reduce bacterial resistance,hence worthy to be popularized in curing bacterial infection clinically.