莫西沙星抑制金黄色葡萄球菌耐药突变体选择的体外PK/PD研究  

In vitro PK/PD study on moxifloxacin to suppress selection of staphylococcus aureus mutant

作　　者：唐云峡[1] 梁蓓蓓[2] 王睿[2] 

机构地区：[1]广西中医药大学附属瑞康医院,广西南宁530011 [2]中国人民解放军总医院药物临床研究中心,北京100853

出　　处：《中国医院药学杂志》2015年第20期1857-1862,共6页Chinese Journal of Hospital Pharmacy

摘　　要：目的：建立体外药效学模型,研究盐酸莫西沙星抑制金黄色葡萄球菌耐药突变体选择的体外PK/PD参数。方法：用琼脂平皿二倍稀释法测定金黄色葡萄球菌102526及105006的MIC、MPC,建立微生物法并测定莫西沙星药物浓度,建立体外药效学模型,用梯形法计算AUC0-t：MIC及AUC0-t：MPC。结果：微生物方法学的精密度RSD〈10%,相对回收率范围为95%~105%。敏感菌102526对莫西沙星的MIC及MPC分别为0.064,0.25 mg·L-1,其主要PK/PD参数AUC0-24/MIC和AUC0-24/MPC分别为307,76.75 mg·h·L-1;Cmax/MIC及Cmax/MPC分别为63.75及15.94。中介耐药菌105006对莫西沙星的MIC和MPC分别为1,8 mg·L-1,其24 hAUC/MIC均远小于125 mg·h·L-1,Cmax/MIC亦小于10。结论：本研究成功建立了体外药效学模型,用其研究莫西沙星对金黄色葡萄球菌的体外抗菌活性,研究中测定了莫西沙星的PK/PD参数和细菌恢复生长曲线,验证了药物浓度处于耐药突变选择窗内时可选择性富集中介耐药菌的耐药突变窗理论。OBJECTIVE To establish an in vitro pharmocodynamic model and study on PK/PD of moxifloxacin to suppress drug resistant mutant of staphylococcus aureus.METHODS Minimal inhibitory concentration（MIC）and mutant prevention concentration（MPC）of moxifloxacin for staphylococcus aureus 102526 and 105006 were determined by agar plate dilution method.Method of microbial assays of antibiotics was used to determine concentration of moxifloxacin,in vitro pharmocodynimic model was used with a pharmacokinetic half life of decline similar to that encountered in humans.AUC/MIC and AUC/MPC were calculated by keystoning method.RESULTS The rsd% of precision were〈10%,recovery was 95%-105%.MIC and MPC of moxifloxacin for staphylococcus aureus strain 102526 were 0.064 and 0.25 mg·L-1,respectively,and its AUC0-24/MIC and AUC0-24/MPC were 307 and 76.75 mg·h·L-1,Cmax/MIC and Cmax/MPC were 63.75 and 15.94.MIC and MPC of moxifloxacin for staphyl ococcus aureus strain 105006 were 1 and 8 mg·L-1,respectively,and its AUC/MIC〈125mg·h·L-1 and Cmax/MIC〈10.CONCLUSION In vitro pharmacodynamic model is successfully established and used in research of antibacterial activity of moxifloxacin for staphylococcus aureus.PK/PD of moxifloxacin is determined to draw curve of log（cfu·ml-1）-time of staphylococcus aureus,and our study has validated MSW hypothesis.

关 键 词：金黄色葡萄球菌 莫西沙星 MIC MPC 微生物法 体外药效学模型 

分 类 号：R965.1[医药卫生—药理学]