The study objective was to evaluate steady-state pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese patients. Fourteen hospitalised patients weighing >120kg received piperacillin/tazobactam 4.5 g every 8 h (q8h) or 6.75 g q8h infused over 4h. Blood samples were collected at steady-state and drug concentrations were determined. Pharmacokinetic parameters were estimated and 5000-patient Monte Carlo simulations were performed for four prolonged-infusion dosing regimens. The probability of target attainment (PTA) for ≥50% fT>MIC was calculated for piperacillin at various MICs, and the PTA for fAUC(0-24)≥96 mg h/L was calculated for tazobactam. Mean±S.D. patient demographics were: age 49±10 years; weight 161±29 kg; and body mass index 52.3±10.8 kg/m(2). For piperacillin and tazobactam, respectively, the mean±S.D. elimination rate was 0.440±0.177 h(-1) and 0.320±0.145 h(-1), volume of distribution was 33.4±14.0L (0.21±0.07L/kg) and 37.5±15.3L (0.23±0.08 L/kg), and systemic clearance was 13.7±5.2L/h and 11.1±4.2L/h. For piperacillin, the PTA was ≥91% for doses ≥4.5g q8h at MICs≤16 μg/mL. For tazobactam, the PTA was 57%, 84% and 94% for doses of 4.5, 6.75 and 9.0g q8h, respectively. The pharmacokinetics of piperacillin and tazobactam are altered in obese patients. To ensure adequate tazobactam concentrations for β-lactamase inhibition, it may be prudent to employ larger initial doses for empirical therapy in obese patients.

译文

:本研究的目的是评估在肥胖患者中长期输注哌拉西林和他唑巴坦的稳态药代动力学和药效学。体重大于120kg的14例住院患者每8小时(q8h)接受4.5 g哌拉西林/他唑巴坦或4h输注6.75 g q8h。以稳态收集血样并确定药物浓度。估计了药代动力学参数,并针对四种延长输液方案进行了5000名患者的Monte Carlo模拟。对于哌拉西林,在各种MIC下计算≥50%fT> MIC的目标达成概率(PTA),对于他唑巴坦计算fAUC(0-24)≥96mg h / L的PTA。平均值±标准差患者人口统计学特征是:年龄49±10岁;体重161±29 kg;体重指数52.3±10.8 kg / m(2)。对于哌拉西林和他唑巴坦,平均值±S.D。消除速度为0.440±0.177 h(-1)和0.320±0.145 h(-1),分布体积为33.4±14.0L(0.21±0.07L / kg)和37.5±15.3L(0.23±0.08 L / kg) ,全身清除率分别为13.7±5.2L / h和11.1±4.2L / h。对于哌拉西林,当MIC≤16μg/ mL时,≥4.5g q8h剂量的PTA≥91%。对于他唑巴坦,每4.5g,6.75和9.0g q8h剂量的PTA分别为57%,84%和94%。肥胖患者的哌拉西林和他唑巴坦的药代动力学发生变化。为了确保适当的他唑巴坦浓度足以抑制β-内酰胺酶,在肥胖患者中以较大的初始剂量进行经验治疗可能是明智的。

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