Pharmacokinetic studies of linezolid and teicoplanin in the critically ill
Pharmacokinetic studies of linezolid and teicoplanin in the critically ill
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DOI：
10.1093/jac/dki014
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发表时间：
2005-03-01
影响因子：
5.2
通讯作者：
Wilson, APR
中科院分区：
文献类型：
--
作者：
Whitehouse, T;Cepeda, JA;Wilson, APR
目的：为了确定利奈唑胺和替考拉宁在危重病Patients.Patients和methods的药代动力学特征：血清经常收集在第0天，然后前和1小时后给药的第1天，第2天，第3天，第5天，第7天，此后每三天在治疗期间。使用HPLC分析血清利奈唑胺浓度。血清替考拉宁水平进行了分析荧光偏振immunoassay.Results：一个二室模型，需要表征利奈唑胺的药代动力学（n=28），并解释多次给药后看到的积累。估计清除率为0.049 +/-0.016 L/h/kg（+/-s.e.m.）。估计）。在稳态（给药间隔12 h）下，600 mg给药后利奈唑胺血清浓度超过4 mg/L的折点持续10.88 h（95% CI 10.09-11.66），AUC/MIC为92.4（95% CI 57.2-127.7）。替考拉宁的最佳描述为二室模型（n=26）。清除率为4.97+/-1.58 L/h。在所有受试者中，整个给药间隔（400 mg剂量，每12小时一次）的血清水平均超过4 mg/L的折点，AUC/MIC为399.3（95% CI 329.6-469.0）。然而，14例中只有4例超过10 mg/L的血清谷浓度。对于这两种药物，谷水平是相似的，在那些谁幸存下来，那些谁dead.Conclusions：利奈唑胺剂量在600毫克，每12小时是足够的，在危重病，而不需要调整肾功能。对于替考拉宁，需要进一步研究以确认谷浓度10 mg/L是否与高于5 mg/L的治愈率相关。如果是这样，则需要进行血清药物测定以确保治疗水平。
Objectives: To determine the pharmacokinetic characteristics of linezolid and teicoplanin in critically ill patients.Patients and methods: 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.Results: 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.Conclusions: 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.