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Dosage Optimization Using Physiologically Based Pharmacokinetic Modeling for Pediatric Patients with Renal

Najia Rahim1, Muhammad Sarfraz2, Abubakar Bello3

  • 1Department of Pharmacy Practice, Dow College of Pharmacy, Dow University of Health Sciences, Karachi, Pakistan. najia.rahim@duhs.edu.pk.

AAPS Pharmscitech
|January 17, 2025
PubMed

Insights

This study developed a physiologically based pharmacokinetic (PBPK) model for meropenem in pediatric patients with renal impairment (RI). The model optimizes meropenem dosing, recommending reduced doses for moderate and severe RI to ensure effective plasma concentrations.

Area of Science:

  • Pharmacokinetics and Drug Metabolism
  • Pediatric Nephrology
  • Computational Pharmacology

Background:

  • Renally eliminated antibiotics' pharmacokinetics are affected by renal function changes in pediatric patients.
  • Limited data exists on meropenem pharmacokinetics in pediatric subjects with renal insufficiency.

Purpose of the Study:

  • To develop a physiologically based pharmacokinetic (PBPK) model for meropenem in pediatric patients.
  • To optimize meropenem dosing in pediatric patients with renal impairment (RI).

Main Methods:

  • A PBPK model was developed using GastroPlus™ 9.9 with literature data.
  • The model was scaled to pediatric patients with varying degrees of RI.
  • Model fit was assessed using average fold errors (AFE) for AUC and Cmax.

Main Results:

  • AFE values for AUC0-t, AUC0-α, and Cmax were 1.60, 1.08, and 1.48, respectively.
  • Recommended meropenem dose reductions to 10 mg/kg for moderate RI and 7.5 mg/kg for severe RI.
  • Optimized doses achieved the target time above minimum inhibitory concentration (MIC) in virtual pediatric populations with RI.

Conclusions:

  • The developed PBPK model quantitatively assesses RI's impact on meropenem pharmacokinetics in pediatrics.
  • This tool aids in optimizing meropenem dosing regimens for pediatric patients with renal impairment.

Keywords:
MeropenemPBPK modelingPediatric patientsRenal impairment

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