乳酸卡德沙星对大鼠肝P450酶活性的影响  

Effect of caderofloxacin lactate on CYP450 activity in rat liver

作　　者：刘荔[1] 刘嵘[2] 吴畅烜 许潇[1] 张冬梅[1] 谢林[1] 刘晓东[1] 

机构地区：[1]中国药科大学药物代谢与动力学研究中心 [2]中国药科大学医药化工研究所,南京210009 [3]南京生命能科技开发有限公司,南京210016

出　　处：《中国药科大学学报》2007年第2期144-148,共5页Journal of China Pharmaceutical University

基　　金：国家高技术研究发展计划资助项目(No.2003AA2Z347A);江苏省药物代谢与动力学重点实验室资助项目(No.BM2001201)~~

摘　　要：目的:研究乳酸卡德沙星对大鼠肝P450酶活性的影响。方法:采用鸡尾酒技术,测定单剂量和多剂量使用乳酸卡德沙星前后大鼠血浆中相应的探针药物咪达唑仑、右美沙芬、奥美拉唑、茶碱、氯唑沙腙和双氯芬酸的浓度及其药代动力学参数。结果:大鼠单剂量给予乳酸卡德沙星后,探针药物的浓度及其药代动力学参数均没有显著性变化。按每天两次,每次9 mg/kg剂量灌胃乳酸卡德沙星,连续12 d后,与用药前比较,咪达唑仑和双氯芬酸的血药浓度及其药代动力学参数未见显著性改变;但奥美拉唑的血药浓度及其AUC0-t有升高的趋势,茶碱的血药浓度及其AUC0-t有降低趋势;右美沙芬的血药浓度和AUC0-t显著升高,而氯唑沙腙的血药浓度和AUC0-t显著降低。结论:单剂量使用乳酸卡德沙星对探针药物的药代动力学行为没有显著性影响。多剂量给予乳酸卡德沙星对大鼠代谢氯唑沙腙的代谢酶有诱导作用,对代谢右美沙芬的代谢酶有抑制作用。Aim： To investigate the effect of caderofloxacin on CYP450 activity in rats. Methods： Six probes （theophylline, midazolam, ehlorzoxazoee, dextromethorphan, omeprazole and dielofenae） were simultaneously given to rats in the absence or the presence of eoadministered eaderofloxaein. The plasma concentrations of the six probes were measured by LC-MS and the pharmaeokinetie parameters were also estimated. Results： Single dosing of eaderofloxaein （9 mg/kg） did not affect the plasma concentrations of six probes and their corresponding pharmaeokinetie parameters. Following multiple dosing of eaderofloxaein （9 mg/kg, orally, twice daily for consecutive 12 days）, the AUC0-t and drug concentration of omeprazole tended to increase but opposite to that of theophylline. However, no statistical significance existed. Meanwhile, compared to the control, the AUC0-t and drug concentration of ehlorzoxazone significantly decreased （P 〈 0.01 ） and the AUC0-t and drug concentration of dextromethorphan significantly increased （P 〈 0.01 ）. Conclusion： Single dosing of eaderofloxaein had very little influence on the activities of CYP450, while multiple dosing of eaderofloxaein tended to induce CYP2E1 activity and inhibit CYP2D activity.

关 键 词：乳酸卡德沙星 鸡尾酒技术 CYP450 

分 类 号：R965[医药卫生—药理学]