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基于清除耐甲氧西林金黄色葡萄球菌所需的血清浓度时间曲线下面积的替考拉宁初始给药方案。

An initial dosing method for teicoplanin based on the area under the serum concentration time curve required for MRSA eradication.

机构信息

Department of Clinical Pharmacy and Pharmacology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.

出版信息

J Infect Chemother. 2011 Apr;17(2):297-300. doi: 10.1007/s10156-010-0105-1. Epub 2010 Aug 17.

Abstract

Teicoplanin is a glycopeptide antibacterial agent that has a long serum half-life and therefore takes time to achieve steady-state conditions. An appropriate initial dosing is needed for teicoplanin to promptly reach an effective serum trough concentration. However, little information is available on tailoring the initial dosing for patients with various characteristics. The objective of this study was to develop a nomogram for determining teicoplanin initial dose to promptly reach an effective trough concentration (≥ 13 μg/mL). A logistic regression analysis was performed to test whether the area under the concentration time curve (AUC) is a significant predictor of microbiological response (persistence 0; eradication 1). The study included 24 adult patients with methicillin-resistant Staphylococcus aureus infections [minimal inhibitory concentration (MIC) for the isolates was <2 μg/mL). Each AUC was estimated using individual dose, creatinine clearance (CL(cr)), and body weight data. The target value, which gives about a 0.9 microbiological eradication probability, was 750 μg h/mL for AUC from zero to 24 h (AUC(0-24 h)). Using published population pharmacokinetic parameters, the dose required to achieve the AUC(0-24 h) target was calculated as dose (mg) = 750 × (0.00498 × CL(cr) (mL/min) + 0.00426 × body weight (kg). For various combinations of CL(cr) and body weight, we checked the calculated doses using a therapeutic drug monitoring (TDM)-supporting software and developed a nomogram. The nomogram would be useful for initial dose adjustment to promptly reach an effective serum trough concentration and avoid adverse events of teicoplanin.

摘要

替考拉宁是一种糖肽类抗菌药物,其血清半衰期较长,因此需要时间达到稳态。替考拉宁需要适当的初始剂量才能迅速达到有效的血清谷浓度。然而,对于具有不同特征的患者,如何调整初始剂量的相关信息有限。本研究的目的是开发一个列线图,以确定替考拉宁的初始剂量,使其迅速达到有效的谷浓度(≥13μg/mL)。采用逻辑回归分析来检验浓度时间曲线下面积(AUC)是否是微生物学反应(持续 0;清除 1)的显著预测因子。该研究纳入了 24 例耐甲氧西林金黄色葡萄球菌感染的成年患者(分离株的最小抑菌浓度(MIC)<2μg/mL)。使用个体剂量、肌酐清除率(CL(cr))和体重数据分别估算每个 AUC。目标值为 750μg h/mL,约为 0.9 微生物清除概率,适用于 0 至 24 小时 AUC(AUC(0-24 h))。使用已发表的群体药代动力学参数,计算达到 AUC(0-24 h)目标所需的剂量为剂量(mg)= 750×(0.00498×CL(cr)(mL/min)+0.00426×体重(kg))。对于 CL(cr)和体重的各种组合,我们使用治疗药物监测(TDM)支持软件检查计算出的剂量,并开发了一个列线图。该列线图将有助于调整初始剂量,以迅速达到有效的血清谷浓度并避免替考拉宁的不良反应。

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