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<p>The pharmacokinetics of renally eliminated antibiotics can be influenced by changes associated with renal function and development in a growing subject. Little is known about the effects of renal insufficiency on the pharmacokinetics of meropenem in pediatric subjects. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of meropenem for pediatric patients that can be used to optimize meropenem dosing in pediatric patients with renal impairment (RI). The PBPK model was developed using GastroPlus™ 9.9 based on clinical data obtained from the literature and then scaled to pediatric patients with RI for dose optimization of meropenem. The goodness of fit of the model was assessed by comparing the predicted values of AUC<sub>0-t</sub>, AUC<sub>0-α</sub>, and C<sub>max</sub> with the observed data and the average fold errors (AFE). The AFE values for AUC<sub>0-t</sub>, AUC<sub>0-α</sub>, and C<sub>max</sub> in the pediatric population were measured to be 1.60, 1.08, and 1.48, respectively. In addition, dose optimization was performed in virtual pediatric populations with varying degrees of RI and a dose reduction to 10&#xa0;mg/kg and 7.5&#xa0;mg/kg was recommended for moderate and severe RI, respectively. In all virtual pediatric populations with RI, the plasma concentration reached the recommended time above the minimum inhibitory concentration (MIC) at all optimized doses. The developed PBPK model for meropenem provides a quantitative tool to assess the impact of RI on the pharmacokinetics of meropenem in pediatric patients, which may be useful for optimizing the dosing regimen.</p> Graphical Abstract <p></p>

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Dosage Optimization Using Physiologically Based Pharmacokinetic Modeling for Pediatric Patients with Renal Impairment: A Case Study of Meropenem

  • 期刊论文

  • 发表日期：

    2025年1月16日

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  • Najia Rahim,
  • Muhammad Sarfraz,
  • Abubakar Bello,
  • Syed Baqir Shyum Naqvi

摘要

The pharmacokinetics of renally eliminated antibiotics can be influenced by changes associated with renal function and development in a growing subject. Little is known about the effects of renal insufficiency on the pharmacokinetics of meropenem in pediatric subjects. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of meropenem for pediatric patients that can be used to optimize meropenem dosing in pediatric patients with renal impairment (RI). The PBPK model was developed using GastroPlus™ 9.9 based on clinical data obtained from the literature and then scaled to pediatric patients with RI for dose optimization of meropenem. The goodness of fit of the model was assessed by comparing the predicted values of AUC0-t, AUC0-α, and Cmax with the observed data and the average fold errors (AFE). The AFE values for AUC0-t, AUC0-α, and Cmax in the pediatric population were measured to be 1.60, 1.08, and 1.48, respectively. In addition, dose optimization was performed in virtual pediatric populations with varying degrees of RI and a dose reduction to 10 mg/kg and 7.5 mg/kg was recommended for moderate and severe RI, respectively. In all virtual pediatric populations with RI, the plasma concentration reached the recommended time above the minimum inhibitory concentration (MIC) at all optimized doses. The developed PBPK model for meropenem provides a quantitative tool to assess the impact of RI on the pharmacokinetics of meropenem in pediatric patients, which may be useful for optimizing the dosing regimen.

Graphical Abstract