体外药动学模型中恩诺沙星对猪大肠杆菌的药效研究

Pharmacodynamic effect of enrofloxacin against Escherichia coli in in vitro pharmacokinetic model

为使畜禽专用的喹诺酮类药物更合理地应用,通过建立体外模型的方法,研究了恩诺沙星对大肠杆菌的药效。结果,在消除半衰期为3 h的模型内,2MIC(最小抑菌浓度)的恩诺沙星对猪大肠杆菌仅能抑制4 h,模型运行4 h后细菌出现再生长。5MIC和8MIC的恩诺沙星对猪大肠杆菌可抑制6 h,模型运行6 h后细菌出现再生长。16MIC的恩诺沙星可在模型运行期间对猪大肠杆菌产生持续的抑制杀灭作用。在消除半衰期为6.5 h的模型内,2MIC的恩诺沙星对猪大肠杆菌仅能抑制4 h,模型运行4 h后细菌出现再生长。5MIC、8MIC和16MIC的恩诺沙星可在模型运行期间对猪大肠杆菌产生持续的抑制杀灭作用,4 h已经不能检测到猪大肠杆菌的存在。结果表明,若要使恩诺沙星发挥持续的抗菌效果,保持Cmax/MIC大于一定数值,同时维持有足够高的AUC0→24/MIC是非常必要的。

For the rational usage of fluoroquinolones in livestock and poultry, an in vitro pharmacokinetic model was used to study pharmacodynamic effect of enrofloxacin against Escherichia coli. In consequence,in the in vitro model with elimination half-life of 3 h,E. coli was inhibited for 4 h by 2MIC enrofloxacin and for 6 h by 5MIC and 8MIC enrofloxacin. E. coli was continuously inhibited in the entire experiment period of 12 h by 16MIC enrofloxacin. In the in vitro model with elimination half-life of 6.5 h,E. coli was inhibited only for 4 h by 2MIC enrofloxacin,and E. coli regrew after the model worked about for 4 h. E. coli was killed by 5MIC,SMIC and 16MIC enrofloxacin. E. coli was not detected after the model worked about for 4 h. It is concluded that Cmax/MIC and AUC0→24/MIC are the most important factors that influence pharmacodynamics of enrofloxacin against E. coli.