Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin
Population pharmacokinetics and limited sampling strategy for first-line tuberculosis drugs and moxifloxacin
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DOI：
10.1016/j.ijantimicag.2014.04.019
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发表时间：
2014-09-01
影响因子：
10.8
通讯作者：
Aarnoutse, R. E.
中科院分区：
文献类型：
--
作者：
Magis-Escurra, C.;Later-Nijland, H. M. J.;Aarnoutse, R. E.
结核病（TB）药物的治疗性药物监测（TDM）目前侧重于峰值血浆浓度，但总暴露量[24小时浓度-时间曲线下面积（AUC(0-24)）]可能与这些药物的疗效最相关。因此，我们评估了所有四种一线结核病药物（利福平、异烟肼、吡嗪酰胺和乙胺丁醇）和莫西沙星的人群AUC（0-24）数据，并制定了有限的抽样策略，以方便地估计AUC（0-24）值。AUC（0-24）和其他药代动力学（PK）参数在两个荷兰结核病转诊中心进行密集的PK采样后确定。采用最佳子集选择多元线性回归得到有限抽样方程。通过折刀分析计算预测误差中位数百分比和绝对预测误差中位数百分比，评价预测的偏倚和不精确程度。利福平、异烟肼、吡嗪酰胺、乙胺丁醇和莫西沙星的几何平均AUC（0-24）值分别为41.1、15.2、380、25.5和33.6 h mg/L。在各个固定的采样点进行有限的采样，可以同时准确预测所有药物的AUC（0-24）值。在没有临床验证的AUC目标值（0-24）的情况下，平均AUC（0-24）值可作为TDM的参考值。有限的AUC采样（0-24）在许多情况下是可行的，并允许在更大的范围内进行时分复用。(C) 2014 Elsevier B.V.与International Society of Chemotherapy。版权所有。
Therapeutic drug monitoring (TDM) of tuberculosis (TB) drugs currently focuses on peak plasma concentrations, yet total exposure [area under the 24-h concentration-time curve (AUC(0-24))] is probably most relevant to the efficacy of these drugs. We therefore assessed population AUC(0-24) data for all four first-line TB drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) as well as moxifloxacin and developed limited sampling strategies to estimate AUC(0-24) values conveniently. AUC(0-24) and other pharmacokinetic (PK) parameters were determined following intensive PK sampling in two Dutch TB referral centres. Best subset selection multiple linear regression was performed to derive limited sampling equations. Median percentage prediction error and median absolute percentage prediction error were calculated via jackknife analysis to evaluate bias and imprecision of the predictions. Geometric mean AUC(0-24) values for rifampicin, isoniazid, pyrazinamide, ethambutol and moxifloxacin were 41.1, 15.2, 380, 25.5 and 33.6 h mg/L, respectively. Limited sampling at various fixed sampling points enabled an accurate and precise prediction of AUC(0-24) values of all drugs separately and simultaneously. In the absence of clinically validated target values for AUC(0-24), average AUC(0-24) values can be used as reference values in TDM. Limited sampling of AUC(0-24) is feasible in many settings and allows for TDM to be performed at a larger scale. (C) 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.