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Jan 16, 2025;26 (1): 38.

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

Najia Rahim, Muhammad Sarfraz, Abubakar Bello, Syed Baqir Shyum Naqvi
Author Information
  1. Najia Rahim: Department of Pharmacy Practice, Dow College of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan. najia.rahim@duhs.edu.pk. ORCID
  2. Muhammad Sarfraz: College of Pharmacy, Al Ain University, Al Ain, United Arab Emirates.
  3. Abubakar Bello: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Wroclaw, Poland.
  4. Syed Baqir Shyum Naqvi: Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, Karachi, Pakistan.
PMID: 39821536 DOI: 10.1208/s12249-024-03026-y

Abstract

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, AUC, and C with the observed data and the average fold errors (AFE). The AFE values for AUC, AUC, and C 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.

Keywords

Meropenem PBPK modeling Pediatric patients Renal impairment

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MeSH Term

Meropenem
Humans
Models, Biological
Child
Anti-Bacterial Agents
Renal Insufficiency
Area Under Curve
Child, Preschool
Dose-Response Relationship, Drug
Adolescent
Computer Simulation
Male

Chemicals

Meropenem
Anti-Bacterial Agents
Journal Article

Word Cloud

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