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Physiologically based pharmacokinetic modeling of cefotaxime to inform pediatric dosing in renal impairment

Najia Rahim1, Muhammad Sarfraz2, Muhammad Wahajuddin3

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

European Journal of Clinical Pharmacology
|July 9, 2026
PubMed

Insights

This study developed a physiological based pharmacokinetic (PBPK) model for cefotaxime (CFT) in pediatric patients with kidney impairment. Model-informed doses were recommended, reducing standard doses by 40% and 52% for moderate and severe impairment, respectively.

Area of Science:

  • Pharmacology
  • Pediatric Nephrology
  • Computational Biology

Background:

  • Cefotaxime (CFT) is a vital third-generation cephalosporin for severe infections.
  • Dosing guidelines for pediatric patients with renal impairment are limited.
  • Physiological based pharmacokinetic (PBPK) modeling can address this gap.

Purpose of the Study:

  • To develop a PBPK model for CFT in pediatric patients.
  • To characterize CFT disposition in pediatric renal impairment.
  • To provide model-informed dose recommendations for this population.

Main Methods:

  • Developed an adult PBPK model for CFT, then scaled it to pediatrics.
  • Incorporated age-related physiological changes using GastroPlus®.
  • Modeled renal impairment by optimizing tubular secretion and glomerular filtration.

Main Results:

  • The PBPK model accurately predicted CFT pharmacokinetics in normal and impaired renal function (fold error 0.84-1.37).
  • Predicted AUC0-∞ increased 1.22-fold (moderate) and 1.89-fold (severe) in renal impairment.
  • Recommended doses were 60% (moderate) and 48% (severe) of the standard pediatric dose.

Conclusions:

  • The PBPK framework enables rational, model-informed dosing of CFT in pediatric patients with renal impairment.
  • Supports evidence-based dose recommendations for high-risk pediatric populations.
  • Highlights the utility of PBPK modeling in pediatric drug therapy optimization.
Abstract

Keywords:
CefotaximeDose recommendationsPBPK modelingRenal impairment

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