Burgess David S, Hall Ronald G
Center for Advancement of Research and Education in Infectious Diseases, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78229, USA.
Clin Ther. 2007 Jul;29(7):1421-7. doi: 10.1016/j.clinthera.2007.07.024.
Until the 2002 approval of levofloxacin 750 mg QD, ciprofloxacin was the fluoroquinolone of choice against Pseudomonas aeruginosa infections.
This study evaluated the AUC:MIC ratios for ciprofloxacin 400 mg BID and TID and levofloxacin 750 mg QD, all administered intravenously, against P. aeruginosa using a Monte Carlo simulation.
Pharmacokinetic data for ciprofloxacin and levofloxacin and 2002 MIC distributions against P. aeruginosa were obtained from studies in healthy volunteers published in the peer-reviewed literature. Pharmacokinetic studies of each agent were identified by separate MEDLINE searches combining the MeSH heading pharmacokinetics with the generic name of the antimicrobial. Only human studies published in English between 1990 and 2001 were included. Included studies also had to meet 3 minimum criteria: evaluation of clinically relevant dosing regimens, use of rigorous study methods, and provision of mean (SD) values for the pharmacokinetic parameters of interest. When multiple studies met these criteria, a single study was selected for each antimicrobial regimen. Pharmacodynamic analysis was performed using a Monte Carlo simulation of 10,000 patients by integrating the pharmacokinetic parameters, their variability, and 2002 MIC distributions for each antimicrobial regimen. The probability of target attainment was determined for each regimen for an AUC:MIC ratio from 0 to 300. A > or =90% probability of target attainment was considered satisfactory.
For ciprofloxacin 400 mg TID and levofloxacin 750 mg QD, the AUC:MIC ratio at the corresponding 2002 Clinical Laboratory Standards Institute break points of 1 and 2 microg/mL were 33 and 34, respectively. The probabilities of target attainment for a free AUC:MIC ratio >90 (equivalent to a total AUC:MIC ratio > or =125) were 47% for ciprofloxacin 400 mg BID, 54% for ciprofloxacin 400 mg TID, and 48% for levofloxacin 750 mg QD.
When pharmacokinetic data from healthy volunteers and 2002 MIC data were used, none of the simulated fluoroquinolone regimens achieved a high likelihood of target attainment against P. aeruginosa.
在2002年批准每日一次750毫克左氧氟沙星之前，环丙沙星是治疗铜绿假单胞菌感染的首选氟喹诺酮类药物。
本研究采用蒙特卡洛模拟法，评估静脉注射的每日两次和三次400毫克环丙沙星以及每日一次750毫克左氧氟沙星针对铜绿假单胞菌的AUC:MIC比值。
环丙沙星和左氧氟沙星的药代动力学数据以及2002年铜绿假单胞菌的MIC分布数据，取自发表于同行评审文献的健康志愿者研究。每种药物的药代动力学研究通过单独的MEDLINE检索确定，将医学主题词表中的药代动力学与抗菌药物通用名相结合。仅纳入1990年至2001年间发表的英文人体研究。纳入研究还必须满足3项最低标准：评估临床相关给药方案、采用严格研究方法以及提供感兴趣的药代动力学参数的均值（标准差）。当多项研究符合这些标准时，每种抗菌方案选择一项研究。通过整合每种抗菌方案的药代动力学参数、其变异性以及2002年的MIC分布，对10000名患者进行蒙特卡洛模拟以进行药效学分析。确定每种方案在AUC:MIC比值从0至300时达到目标的概率。达到目标的概率≥90%被认为是令人满意的。
对于每日三次400毫克环丙沙星和每日一次750毫克左氧氟沙星，在2002年临床实验室标准协会相应的1和2微克/毫升折点处，AUC:MIC比值分别为33和34。游离AUC:MIC比值>90（相当于总AUC:MIC比值≥125）时，每日两次400毫克环丙沙星达到目标的概率为47%，每日三次400毫克环丙沙星为54%，每日一次750毫克左氧氟沙星为48%。
当使用健康志愿者的药代动力学数据和2002年的MIC数据时，模拟的氟喹诺酮类方案中没有一种对铜绿假单胞菌达到目标的可能性很高。
