氟氧头孢对临床菌株的药代动力学及药效学研究  

Pharmacokinetic and pharmacodynamic analysis of flomoxef against the clinical isolates of strains

作　　者：冀希炜[1] 吕媛[1] 李耘[1] 卢炜[2] 

机构地区：[1]北京大学第一医院临床药理研究,北京100191 [2]北京大学医学部药学院,北京100191

出　　处：《中国临床药理学杂志》2017年第11期1007-1012,共6页The Chinese Journal of Clinical Pharmacology

摘　　要：目的通过对氟氧头孢体外抗菌活性数据、蛋白结合率数据、人体药代动力学参数进行药代动力学/药效学(PK/PD)相关性分析,评价不同给药方案时氟氧头孢的PK/PD参数。方法用给药间隔期药物浓度超过最低抑菌浓度的时间百分比(%f T_(>MIC))数据作为与氧氟头孢药效相关的PK/PD指标。用计算出的不同%fT_(>MIC)的目标达成分数(TA%)评估药效。对1 g q6 h,1 g q8 h,1 g q12 h,2 g q12 h氧氟头孢的PK/PD参数(%fT_(>MIC))相应值进行相互比较。最佳给药方案选择:用NONMEM软件,通过蒙特卡罗方法模拟各产生1000个患者群体的数据,考察每一个给药方案对于每一种菌株的药效。结果 1 g q12 h,1 g q8 h,1 g q6 h,输注1 h,对产超广谱β内酰胺酶(ESBL)大肠埃希菌70%fT_(>MIC)达到率分别为66.8%,93.8%和89.1%;对产ESBL肺炎克雷伯菌70%fT_(>MIC)达到率分别为62.3%,78.7%和81.8%。2 g q12 h给药,50%和70%fT_(>MIC)达到率与q8 h或q6 h类似。但更高的抗菌药效指标达成概率2.0 g q12 h给药不如1 g q8 h或1 g q6 h。对甲氧西林敏感金黄色葡萄球菌和甲氧西林敏感表皮葡萄球菌等都具有很好的PK/PD特点。结论氟氧头孢作为时间依赖性抗菌药物,无论缩短给药间隔还是延长输液时间,都可一定程度提高疗效。但与延长输注时间相比,尤以缩短给药间隔作用显著。Objective To evaluate the optimal administration regimen of flomoxef for the bacterial infection based on pharmacokinetic/pharmacodynamic（PK/PD） models.Methods A literature search was conducted in Pub Med to capture the pharmacokinetic data of flomoxef.Minimum inhibitory concentrations（MICs） were determined using two-fold agar dilution method.The percent time that drug concentration exceeds the minimum inhibitory concentration（% fT〉MIC） was used as the PK/PD indicator correlated with efficacy.Monte Carlo simulation was employed to determine the appropriate regimens of flomoxef based on the probability of target attainment（PTA） against the clinical isolates of strains.Results The regimens of 1 g q6 h,1 g q8 h and 1 g q12 h with 1 hour infusion at 70% of % fT〉MICachieved 93.1%,89.1% and 66.8% of PTA against Escherichia coli（ESBL＋）,respectively.For the Klebsiella pneumoniae（ESBL＋）, these regimens achieved 81.8%,78.7% and62.3% of PTA at % fT〉MIC= 70%.The regimen of 2 g q12 h achieved the similar PTA as 1g q6 h and 1 g q8 h at 50% and 70% of % fT〉MIC,but not at higher % fT〉MIC.Furthermore,flomoxef also showed potent bactericidal activity against Escherichia coli（ESBL-）,Klebsiella pneumoniae（ESBL-）,methicillin-susceptible S.aureus（MSSA）,methicillin-susceptible S.Epidermidis（MSSE） and Moraxella catarrhalis,etc.with all dosing regimens according to the PK/PD analysis.Conclusion As a time-dependent antibiotic,the clinical outcome of flomoxef can be improved by shortening dosing interval,extending infusion time and/or increasing dose.The first two strategies played more significant roles.

关 键 词：氟氧头孢 药代动力学/药效学 剂量设计 抗菌药效指标达成概率 蒙特卡罗模拟 

分 类 号：R978.1[医药卫生—药品]