Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis - caution with trough concentrations
Therapeutic drug monitoring of once daily tobramycin in cystic fibrosis - caution with trough concentrations
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DOI：
10.1016/j.jcf.2006.05.015
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发表时间：
2007-04-01
影响因子：
5.2
通讯作者：
Turnidge, John
中科院分区：
文献类型：
--
作者：
Coulthard, Kingsley P.;Peckham, Daniel G.;Turnidge, John
背景：每天一次静脉注射氨基糖苷类药物（ODD）被广泛用于治疗囊性纤维化患者的铜绿假单胞菌急性加重。关于此类治疗的最合适的治疗药物监测 (TDM) 方法是什么，存在争议，建议包括血浆谷浓度 < 1 mg/L 或 < 2 mg/L、曲线下面积 (AUC) 和各种列线图。本研究旨在使用 AUC 和槽 TDM 方法比较患有囊性纤维化的成人和儿童中妥布霉素的 ODD 暴露。方法：使用单指数软件程序根据 2 个血浆浓度计算 AUC，在 22 名服用前妥布霉素浓度 < 1 mg/L 的成人中测定 AUC。 5 名妥布霉素清除率降低的儿童的暴露量按通常推荐剂量 10 mg/kg/天进行模拟，但保留谷值 < 1 mg/L。结果：在这些血清肌酐正常且谷值浓度 < 1 mg/L 的患者中，妥布霉素剂量为 10 mg/kg 的妥布霉素导致暴露量超过与常规 8 小时给药相关的暴露量。 结论：与传统的每 8 小时妥布霉素给药一样，谷值 < mg/L 与 ODD 无关。 (C) 2006 年欧洲囊性纤维化协会。由 Elsevier B.V. 出版。保留所有权利。
Background: Once daily intravenous aminoglycoside dosing (ODD) is widely used to treat acute Pseudomonas aeruginosa exacerbations in patients with cystic fibrosis. Controversy exists as to what is the most appropriate method of therapeutic drug monitoring (TDM) of such therapy with recommendations including trough plasma concentrations of < 1 mg/L or < 2 mg/L, area under curve (AUC) and various nomograms. This study aimed to compare the exposures to ODD of tobramycin in adults and children with cystic fibrosis using the AUC and trough TDM approaches.Methods: Using a mono-exponential software program to calculate AUC from 2 plasma concentrations, AUCs were determined in 22 adults with pre-dose tobramycin concentrations < 1 mg/L. The exposure of 5 children with reduced tobramycin clearances was simulated at the usual recommended dose of 10 mg/kg/daily but retaining a trough < 1 mg/L.Results: A tobramycin dose of 10 mg/kg of tobramycin in these patients with normal serum creatinine and a trough concentration < 1 mg/L resulted in exposures in excess of those associated with conventional 8-hourly dosing.Conclusions: The TDM approach of a trough < mg/L, as used with conventional 8-hourly tobramycin dosing, is not relevant to ODD. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.