Optimization of gabapentin dosage in pediatric patients with renal impairment: a physiologically based pharmacokinetic modeling approach
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Le résumé fourni par la source
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, AUC0- ∞ 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.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Optimization of gabapentin dosage in pediatric patients with renal impairment: a physiologically based pharmacokinetic modeling approach
- Date Crossref
- 26/09/2025
- Éditeur
- Frontiers Media SA
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Third People's Hospital of Chengdu pays non établi dans la noticeÉtablissement de santé
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Southwest Jiaotong University Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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Sichuan University pays non établi dans la noticeUniversité ou école supérieure
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Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital pays non établi dans la noticeÉtablissement de santé
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West China School of Pharmacy Department of Clinical Pharmacy and Pharmacy Administration pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine Department of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
Third People's Hospital of Chengdu, Department of Pharmacy — Southwest Jiaotong University et Sichuan University, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.