Department of Pharmacy, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
J Glob Antimicrob Resist. 2023 Dec;35:347-353. doi: 10.1016/j.jgar.2023.08.003. Epub 2023 Sep 4.
Several linezolid population pharmacokinetic (popPK) models have been established to facilitate optimal therapy; however, their extrapolated predictive performance to other clinical sites is unknown. This study aimed to externally evaluate the predictive performance of published pharmacokinetic models of linezolid in adult patients.
For the evaluation dataset, 150 samples were collected from 70 adult patients (72.9% of which were critically ill) treated with linezolid at our center. Twenty-five published popPK models were identified from PubMed and Embase. Model predictability was evaluated using prediction-based, simulation-based, and Bayesian forecasting-based approaches to assess model predictability.
Prediction-based diagnostics found that the prediction error within ±30% (F) was less than 40% in all models, indicating unsatisfactory predictability. The simulation-based prediction- and variability-corrected visual predictive check and normalized prediction distribution error test indicated large discrepancies between the observations and simulations in most of the models. Bayesian forecasting with one or two prior observations significantly improved the models' predictive performance.
The published linezolid popPK models showed insufficient predictive ability. Therefore, their sole use is not recommended, and incorporating therapeutic drug monitoring of linezolid in clinical applications is necessary.
已建立了多个利奈唑胺群体药代动力学（popPK）模型以促进优化治疗；然而，其对其他临床场所的外推预测性能尚不清楚。本研究旨在对外科成人患者利奈唑胺已发表的药代动力学模型的预测性能进行评估。
在评价数据集方面，从本中心接受利奈唑胺治疗的 70 例成人患者（其中 72.9%为危重症患者）中采集了 150 个样本。从 PubMed 和 Embase 中确定了 25 个已发表的 popPK 模型。采用基于预测、基于模拟和基于贝叶斯预测的方法来评估模型的预测性能，从而评估模型的预测能力。
基于预测的诊断发现，所有模型中预测误差在±30%（F）以内的比例均小于 40%，表明预测能力不理想。基于模拟的预测和变异性校正的可视化预测检查和归一化预测分布误差检验表明，大多数模型的观察值和模拟值之间存在较大差异。使用一个或两个先验观察值进行贝叶斯预测可以显著改善模型的预测性能。
已发表的利奈唑胺 popPK 模型显示出不足的预测能力。因此，不建议单独使用，在临床应用中需要进行利奈唑胺的治疗药物监测。
