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

Xiaoli Qin; Chaozhuang Shen; Zhimin Li; Yujie Yang

doi:10.3389/fphar.2025.1669990

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

Front Pharmacol. 2025 Sep 26:16:1669990. doi: 10.3389/fphar.2025.1669990. eCollection 2025.

Authors

Xiaoli Qin¹, Chaozhuang Shen², Zhimin Li³, Yujie Yang¹

Affiliations

¹ Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.
² Department of Clinical Pharmacy and Pharmacy Administration, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.
³ Department of Pharmacy, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

Abstract

Background: Gabapentin (GAB) is an adjunctive antiepileptic drug widely used in pediatric patients. However, little is known about its pharmacokinetics in pediatric patients under 3 years old or with renal impairment (RI). To address this, we developed a physiologically based pharmacokinetic (PBPK) model for precise dosing guidance.

Methods: A PBPK model for GAB was first developed in healthy adults using PK-Sim® and then extended to pediatric populations, accounting for age-related physiological changes. For RI simulations, reduced glomerular filtration and tubular secretion were incorporated based on adult RI models.

Results: The PBPK model accurately predicted GAB exposure in adults and children after single and multiple administration (geometric mean fold error <2). Plasma concentrations and PK parameters were similar in children under 3 years old and those aged 3-12. In pediatric RI patients under 12 years old, AUC_0- ${}_{\infty}$ increased to 2.09-, 3.30-, and 31.67-fold for mild, moderate, and severe RI, respectively, compared to healthy children. Dosing frequency was adjusted to bid (mild RI), qd (moderate RI), and qod (severe RI), with an additional 50% dose reduction for severe RI.

Conclusion: PBPK models provide better guidance for GAB dosing in pediatric patients with varying RI degrees, laying a foundation for precision therapy. This study is a significant step in optimizing GAB treatment for this high-risk pediatric population.

Keywords: dose adjustment; gabapentin; pediatric; physiologically based pharmacokinetic; renal impairment.