Whitehouse Tony, Cepeda Jorge A, Shulman Rob, Aarons Leon, Nalda-Molina Ricardo, Tobin Caroline, MacGowan Alasdair, Shaw Steve, Kibbler Chris, Singer Mervyn, Wilson A Peter R
Bloomsbury Institute of Intensive Care Medicine, Department of Medicine, University College London, London, UK.
J Antimicrob Chemother. 2005 Mar;55(3):333-40. doi: 10.1093/jac/dki014. Epub 2005 Feb 10.
To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients.
Serum was collected frequently during day 0 and then pre- and 1 h post-dose on days 1, 2, 3, 5, 7 and every third day thereafter during treatment. Serum linezolid concentrations were analysed using HPLC. Serum teicoplanin levels were analysed by fluorescence polarization immunoassay.
A two-compartment model was required to characterize linezolid pharmacokinetics (n=28) and account for the accumulation seen after multiple dosing. The estimated clearance was 0.049 +/-0.016 L/h/kg (+/-s.e.m. of estimate). At steady state (dosing interval 12 h), linezolid serum concentrations exceeded the breakpoint of 4 mg/L for 10.88 h (95% CI 10.09-11.66) after a 600 mg dose with an AUC/MIC of 92.4 (95% CI 57.2-127.7). Teicoplanin was best described by a two-compartment model (n=26). The clearance was 4.97+/-1.58 L/h. Serum levels exceeded the breakpoint of 4 mg/L for the entire dosing interval in all subjects (400 mg dose every 12 h) with an AUC/MIC of 399.3 (95% CI 329.6-469.0). However, only four of 14 exceeded trough serum concentrations of 10 mg/L. For both agents, trough levels were similar in those who survived and those who died.
Linezolid dosage at 600 mg every 12 h was adequate in the critically ill without need for adjustment for renal function. For teicoplanin, further study is needed to confirm if a trough of 10 mg/L is associated with a higher rate of cure than 5 mg/L. If so, serum drug assays would be needed to ensure a therapeutic level.
确定利奈唑胺和替考拉宁在重症患者中的药代动力学特征。
在第0天频繁采集血清，然后在治疗期间的第1、2、3、5、7天以及此后每隔三天给药前和给药后1小时采集血清。使用高效液相色谱法分析血清利奈唑胺浓度。通过荧光偏振免疫分析法分析血清替考拉宁水平。
需要一个二室模型来描述利奈唑胺的药代动力学（n = 28）并解释多次给药后出现的蓄积情况。估计清除率为0.049±0.016 L/h/kg（估计值的±标准误）。在稳态（给药间隔12小时）时，600 mg剂量的利奈唑胺血清浓度超过4 mg/L的断点达10.88小时（95%置信区间10.09 - 11.66），AUC/MIC为92.4（95%置信区间57.2 - 127.7）。替考拉宁最好用二室模型描述（n = 26）。清除率为4.97±1.58 L/h。在所有受试者中（每12小时400 mg剂量），血清水平在整个给药间隔内均超过4 mg/L的断点，AUC/MIC为399.3（95%置信区间329.6 - 469.0）。然而，14名患者中只有4名超过了10 mg/L的谷浓度。对于这两种药物，存活者和死亡者的谷浓度相似。
在重症患者中，每12小时600 mg的利奈唑胺剂量足够，无需根据肾功能进行调整。对于替考拉宁，需要进一步研究以确认10 mg/L的谷浓度是否比5 mg/L具有更高的治愈率。如果是这样，则需要进行血清药物检测以确保达到治疗水平。
