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Optimization of gabapentin dosage in pediatric patients with renal impairment: a physiologically based

Xiaoli Qin1, Chaozhuang Shen2, Zhimin Li3

  • 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.

Frontiers in Pharmacology
|October 13, 2025
PubMed

Insights

A new physiologically based pharmacokinetic (PBPK) model accurately predicts gabapentin (GAB) exposure in children, guiding precise dosing for those with renal impairment (RI). This optimizes treatment for a high-risk pediatric population.

Area of Science:

  • Pharmacokinetics
  • Pediatric Pharmacology
  • Computational Modeling

Background:

  • Gabapentin (GAB) is an antiepileptic drug used in children, but its pharmacokinetics in young children and those with renal impairment (RI) are not well understood.
  • Accurate dosing guidance is crucial for effective and safe GAB treatment in pediatric populations.

Purpose of the Study:

  • To develop a physiologically based pharmacokinetic (PBPK) model for gabapentin (GAB).
  • To provide precise dosing guidance for pediatric patients, particularly those with varying degrees of renal impairment (RI).

Main Methods:

  • A PBPK model for GAB was developed in adults using PK-Sim® and adapted for pediatric populations.
  • Age-related physiological changes and reduced renal function in RI were incorporated into the model.
  • Model predictions were validated against existing pharmacokinetic data.

Main Results:

  • The PBPK model accurately predicted GAB exposure in both adult and pediatric populations.
  • Gabapentin pharmacokinetics were similar in children under 3 years and those aged 3-12 years.
  • In pediatric patients with RI, AUC increased significantly with severity: 2.09-fold (mild), 3.30-fold (moderate), and 31.67-fold (severe).
  • Recommended dosing adjustments for RI included bid (mild), qd (moderate), and qod (severe) with a 50% dose reduction for severe RI.

Conclusions:

  • Physiologically based pharmacokinetic (PBPK) models offer improved dosing guidance for gabapentin (GAB) in pediatric patients with renal impairment (RI).
  • This study establishes a foundation for precision therapy in a vulnerable pediatric population requiring GAB treatment.
Abstract

Keywords:
dose adjustmentgabapentinpediatricphysiologically based pharmacokineticrenal impairment

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