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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 pharmacokinetics / pharmacodynamics (PK / PD) correlation of antibacterial activity data, protein binding rate data and human pharmacokinetic parameters in vitro, and to evaluate the efficacy of cefotaxime PK / PD parameters. Methods The percentage of time (% f T _ (& gt; MIC)) drug concentration over the minimum inhibitory concentration at the interval between administrations was used as a PK / PD index associated with oxyfluorocephalosporine efficacy. Efficacy was assessed using the calculated target achieved scores (TA%) for different% fT _ (> MIC). The PK / PD parameters (% fT_ (> MIC)) of 1 g q6 h, 1 g q8 h, 1 g q12 h, 2 g q12 h were compared with each other. Choice of optimal dosing regimen: Using the NONMEM software, data from each of 1,000 patient populations generated by the Monte Carlo method were simulated to examine the efficacy of each dosing regimen for each of the strains. Results The rates of achieving 70% fT (> MIC) of ESBL-producing Escherichia coli at 1 g q12 h, 1 g q8 h, 1 g q6 h and 1 h infusion were 66.8% , 93.8% and 89.1%, respectively. The rates of achieving 70% fT_ (> MIC) of ESBL-producing Klebsiella pneumoniae were 62.3%, 78.7% and 81.8% respectively. At 2 g q12 h dosing, 50% and 70% fT _ (> MIC) attainment rates were similar to q8 h or q6 h. However, the higher antimicrobial efficacy index reached a probability of 2.0 g q12 h, which was inferior to that of 1 g q8 h or 1 g q6 h. Methicillin-sensitive Staphylococcus aureus and methicillin-sensitive Staphylococcus epidermidis have good PK / PD characteristics. Conclusion As a time-dependent antibacterial drug, Fluorooxy cephalosporins can improve the curative effect to a certain extent, no matter shorten the interval of administration or prolong the infusion time. However, compared with prolonged infusion time, especially in shortening the interval of administration significantly.