Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia.
Int J Antimicrob Agents. 2013 Jul;42(1):90-3. doi: 10.1016/j.ijantimicag.2013.02.023. Epub 2013 Apr 13.
Meropenem and piperacillin are two commonly prescribed antibiotics in critically ill surgical patients. To date, the pharmacokinetics of these antibiotics in the presence of indwelling abdominal surgical drains is poorly defined. This was a prospective pharmacokinetic study of meropenem and piperacillin. Serial plasma, urine and surgical drain fluid samples were collected over one dosing interval of antibiotic treatment in ten patients (meropenem, n = 5; piperacillin n = 5). Drug concentrations were measured using a validated high-performance liquid chromatography assay. Median (interquartile range) pharmacokinetic parameter estimates for meropenem were as follows: area under concentration-time curve (AUC), 128.7 mgh/L (95.3-176.7 mgh/L); clearance (CL), 5.7 L/h (5.1-10.5 L/h); volume of distribution (Vd), 0.41 L/kg (0.35-0.56 L/kg); AUC ratio (drain:plasma), 0.2 (0.1-0.2); and calculated antibiotic clearance via surgical drain, 3.8% (2.8-5.4%). For piperacillin, unbound pharmacokinetic results were as follows; AUC, 344.3 mgh/L (341.1-348.4 mgh/L); CL, 13.1 L/h (12.9-13.2 L/h); Vd, 0.63 L/kg (0.38-1.28 L/kg); AUC ratio (drain:plasma), 0.2 (0.2-0.3); and calculated antibiotic clearance via surgical drain 8.2% (3.3-14.0%). A linear correlation was present between the percentage of antibiotic cleared through the drain and the volume of surgical drain fluid output for meropenem (r(2) = 0.89; P = 0.05) and piperacillin (r(2) = 0.63; P = 0.20). Meropenem and piperacillin have altered pharmacokinetics in critically ill patients with indwelling surgical drains. We propose that only when very high drain fluid output is present (>1000 mL/day) would an additional dose of antibiotic be necessary.
美罗培南和哌拉西林是危重症外科患者常用的两种抗生素。迄今为止，这些抗生素在留置腹腔引流管时的药代动力学特性还没有明确界定。这是一项关于美罗培南和哌拉西林的前瞻性药代动力学研究。在十名患者（美罗培南 n = 5；哌拉西林 n = 5）的一个抗生素治疗剂量间隔期间，连续采集了血浆、尿液和外科引流液样本。使用经过验证的高效液相色谱法测定药物浓度。美罗培南的中位（四分位间距）药代动力学参数估计值如下：浓度-时间曲线下面积（AUC），128.7 mgh/L（95.3-176.7 mgh/L）；清除率（CL），5.7 L/h（5.1-10.5 L/h）；分布容积（Vd），0.41 L/kg（0.35-0.56 L/kg）；AUC 比值（引流液：血浆），0.2（0.1-0.2）；通过外科引流计算的抗生素清除率，3.8%（2.8-5.4%）。对于哌拉西林，未结合的药代动力学结果如下：AUC，344.3 mgh/L（341.1-348.4 mgh/L）；CL，13.1 L/h（12.9-13.2 L/h）；Vd，0.63 L/kg（0.38-1.28 L/kg）；AUC 比值（引流液：血浆），0.2（0.2-0.3）；通过外科引流计算的抗生素清除率，8.2%（3.3-14.0%）。美罗培南（r(2) = 0.89；P = 0.05）和哌拉西林（r(2) = 0.63；P = 0.20）通过引流管清除的抗生素百分比与外科引流液输出量之间存在线性相关性。在留置外科引流管的危重症患者中，美罗培南和哌拉西林的药代动力学发生了改变。我们建议，只有当引流液输出量非常高（>1000 mL/天）时，才需要额外给予抗生素剂量。
