Department of Pharmacy, Nanjing Drum Tower Hospital, China Pharmaceutical University, Nanjing, China.
Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing Drum Tower Hospital Clinical College, Nanjing University of Chinese Medicine, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
Eur J Clin Pharmacol. 2024 Sep;80(9):1295-1304. doi: 10.1007/s00228-024-03702-9. Epub 2024 May 27.
To assess the pharmacokinetics and pharmacodynamics of linezolid in a retrospective cohort of hospitalized Chinese older patients.
Patients > 60 years of age, who received intravenous linezolid (600 mg), were included. A population pharmacokinetics (PPK) model was established using nonlinear mixed-effects modeling. The predictive performance of the final model was assessed using goodness-of-fit plots, bootstrap analyses, and visual predictive checks. Monte Carlo simulations were used to evaluate the achievement of a pharmacodynamics target for the area under the serum concentration-time curve/minimum inhibitory concentration (AUC/MIC).
A total of 210 samples were collected from 120 patients. A one-compartment PPK model with linear elimination best predicted the linezolid plasma concentrations. Linezolid clearance (CL) was 4.22 L h and volume of distribution (V) was 45.80 L; serum uric acid (SUA) was a significant covariate of CL.
The results of this study indicated that the standard dose was associated with a risk of overexposure in older patients, particularly those with high SUA values; these patients would benefit from a lower dose (300 mg every 12 h).
评估住院中国老年患者群体中线扎罗定的药代动力学和药效学。
纳入年龄>60 岁、接受静脉注射利奈唑胺（600mg）的患者。采用非线性混合效应模型建立群体药代动力学（PPK）模型。使用拟合度图、自举分析和可视化预测检查来评估最终模型的预测性能。使用蒙特卡罗模拟评估血清浓度-时间曲线下面积/最小抑菌浓度（AUC/MIC）的药效学目标的达成情况。
从 120 名患者中收集了 210 个样本。具有线性消除的单室 PPK 模型可最佳预测利奈唑胺的血浆浓度。利奈唑胺清除率（CL）为 4.22L/h，分布容积（V）为 45.80L；血清尿酸（SUA）是 CL 的重要协变量。
本研究结果表明，标准剂量与老年患者（尤其是 SUA 值较高的患者）药物暴露过度的风险相关；这些患者将受益于较低的剂量（每 12 小时 300mg）。
