Kim Myo-Kyoung, Capitano Blair, Mattoes Holly M, Xuan Dawei, Quintiliani Richard, Nightingale Charles H, Nicolau David P
Department of Pharmacy Research, Hartford Hospital, Connecticut 06102, USA.
Pharmacotherapy. 2002 May;22(5):569-77. doi: 10.1592/phco.22.8.569.33209.
To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin-tazobactam against commonly encountered pathogens. The regimens compared were piperacillin 4.0 g-tazobactam 0.5 g administered every 8 hours, and piperacillin 3.0 g-tazobactam 0.375 g administered every 6 hours.
Multiple-dose, open-label, randomized, crossover study.
Clinical research center at Hartford Hospital.
Twelve healthy volunteers.
The two dosing regimens for piperacillin-tazobactam were administered intravenously in crossover design. Blood was sampled after the third dose.
Drug concentrations were determined by a validated high-performance liquid chromatography assay. The percentage of time above minimum inhibitory concentration (%T>MIC) for piperacillin was calculated for a range of MIC values. The maximum concentration (Cmax), area under the concentration-time curve (AUC0-tau), and total clearance of piperacillin differed significantly between the two study regimens, as did the Cmax, AUC0-tau, volume of distribution, and total clearance of tazobactam (p<0.05). The piperacillin 4.0 g-tazobactam 0.5 g regimen provided 40-50% T>MIC for MIC values 8-16 microg/ml; a similar value for the piperacillin 3.0 g-tazobactam 0.375 g regimen was 16-32 microg/ml.
Although statistically significant differences in the pharmacodynamic profile were noted for the regimens, both provide adequate T>MIC against commonly encountered pathogens considered susceptible to piperacillin-tazobactam. However, for treatment of Pseudomonas aeruginosa infection, combination therapy or higher-dosage regimens (e.g., piperacillin 3.0 g-tazobactam 0.375 g every 4 hours, piperacillin 4.0 g-tazobactam 0.5 g every 6 hours, or continuous-infusion piperacillin 12 g-tazobactam 1.5 g/day) may be a prudent option when full MIC data are unavailable.
比较哌拉西林-他唑巴坦两种给药方案针对常见病原体的药代动力学和药效学特征。所比较的方案为每8小时静脉注射哌拉西林4.0 g-他唑巴坦0.5 g，以及每6小时静脉注射哌拉西林3.0 g-他唑巴坦0.375 g。
多剂量、开放标签、随机、交叉研究。
哈特福德医院临床研究中心。
12名健康志愿者。
采用交叉设计静脉注射两种哌拉西林-他唑巴坦给药方案。在第三次给药后采集血样。
通过经过验证的高效液相色谱法测定药物浓度。针对一系列最低抑菌浓度（MIC）值计算哌拉西林高于最低抑菌浓度的时间百分比（%T>MIC）。两种研究方案中哌拉西林的最大浓度（Cmax）、浓度-时间曲线下面积（AUC0-tau）和总清除率存在显著差异，他唑巴坦的Cmax、AUC0-tau、分布容积和总清除率也存在显著差异（p<0.05）。对于MIC值为8-16μg/ml，哌拉西林4.0 g-他唑巴坦0.5 g方案的%T>MIC为40%-50%；哌拉西林3.0 g-他唑巴坦0.375 g方案的类似值为16%-32%。
虽然两种给药方案在药效学特征上存在统计学显著差异，但二者针对被认为对哌拉西林-他唑巴坦敏感的常见病原体均能提供足够的%T>MIC。然而，对于铜绿假单胞菌感染的治疗，当没有完整的MIC数据时，联合治疗或更高剂量方案（如每4小时使用哌拉西林3.0 g-他唑巴坦0.375 g、每6小时使用哌拉西林4.0 g-他唑巴坦0.5 g或每日持续输注哌拉西林12 g-他唑巴坦1.5 g）可能是谨慎的选择。
