Precision Dosing of Meropenem in Adults with Normal Renal Function: Insights from a Population Pharmacokinetic and Monte Carlo Simulation Study

Yong Kyun Kim, Gaeun Kang, Dae Young Zang, Dong Hwan Lee
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Abstract

This study aimed to develop a population pharmacokinetic (PK) model for meropenem in healthy adults and explore optimal dosing regimens for patients with normal renal function. PK samples were obtained from 12 healthy participants, which were analyzed using noncompartmental analysis and nonlinear mixed-effect modeling. The PK profiles of meropenem were characterized using a two-compartment model, and serum creatinine level was identified as a significant covariate affecting total clearance. Monte Carlo simulations were conducted using this model to inform dosing recommendations. The target index for meropenem efficacy was defined as the cumulative percentage over 24 h during which free (f) drug concentration exceeded the minimum inhibitory concentration (MIC) under steady state conditions (fT>MIC). These simulations indicated that the current dosage regimen of 1 g for 30 min infusions every 8 h achieved a 90% probability of target attainment (PTA) for 40%fT>MIC when the MIC was <2 mg/L. However, to achieve more stringent therapeutic targets, such as a 90%PTA for 100%fT>MIC or a 90%PTA for 100%fT>4MIC, higher doses administered as 3 h extended infusions or as continuous infusions may be necessary. These results highlight the need for model-informed precision dosing to enhance the efficacy of meropenem therapy across various MIC levels and therapeutic targets.
肾功能正常成人的美罗培南精确剂量:群体药代动力学和蒙特卡罗模拟研究的启示
本研究旨在建立美罗培南在健康成人中的群体药代动力学(PK)模型,并探索肾功能正常患者的最佳给药方案。研究人员采集了 12 名健康参与者的 PK 样本,并采用非室分析和非线性混合效应模型对其进行了分析。使用双室模型分析了美罗培南的 PK 曲线,发现血清肌酐水平是影响总清除率的重要协变量。利用该模型进行了蒙特卡罗模拟,为用药建议提供依据。美罗培南疗效的目标指数被定义为在稳态条件下,24 小时内游离(f)药物浓度超过最小抑菌浓度(MIC)的累积百分比(fT>MIC)。这些模拟结果表明,目前每 8 小时输注 1 克、每次 30 分钟的剂量方案在 MIC 为 MIC 时,40%fT>MIC 的达标概率 (PTA) 为 90%,100%fT>4MIC 的达标概率 (PTA) 为 90%。这些结果突出表明,需要根据模型进行精确给药,以提高美罗培南在不同 MIC 水平和治疗靶点上的疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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