ArticleClinical pharmacokinetics2015
A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation.
Article in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Clinical Pharmacokinetic Monitoring of Free Valproic Acid Levels: A Systematic Review.Clinical pharmacokinetics · 2022Pooled it
- A systematic review of population pharmacokinetics of valproic acid.British journal of clinical pharmacology · 2018Pooled it
- Virtual Twin Approach Using Physiologically Based Pharmacokinetic Modeling to Support Precision Dosing of Valproic Acid in Geriatric Patients.Clinical pharmacology and therapeutics · 2026Article
- Personalized prediction of initial valproic acid dose in children with epilepsy using machine learning techniques.International journal of clinical pharmacy · 2026Article
- Bayesian-Based Pharmacokinetic Framework Integrated with Therapeutic Drug Monitoring for Assessing Adherence to Antiseizure Medications: A Clinical Trial Simulation Study.Journal of medical Internet research · 2026Article
- Physiologically Based Pharmacokinetic Modeling-Based Evaluation of Current Carbamazepine and Valproic Acid Dosing Guidelines for Pediatric Epilepsy Treatment.Paediatric drugs · 2025Article
- Phase 1 study of quercetin, a natural antioxidant for children and young adults with Fanconi anemia.Blood advances · 2025Article
- Prediction Trough Concentrations of Valproic Acid Among Chinese Adult Patients with Epilepsy Using Machine Learning Techniques.Pharmaceutical research · 2025Article
- Fixed parameters in the population pharmacokinetic modeling of valproic acid might not be suitable: external validation in Chinese adults with epilepsy or after neurosurgery.European journal of clinical pharmacology · 2024Article
- Predictors of valproic acid steady-state serum levels in adult and pediatric psychiatric inpatients: a comparative analysis.Psychopharmacology · 2024Article
- Population pharmacokinetics of valproic acid in children with epilepsy: Implications for dose tailoring when switching from oral syrup to sustained-release tablets.CPT: pharmacometrics & systems pharmacology · 2024Article
- Article
- Combined carbapenem resulted in a 4.48-fold increase in valproic acid clearance: a population pharmacokinetic model in Chinese children and adults with epilepsy or after neurosurgery.Frontiers in pharmacology · 2024Article
- Handling Delayed or Missed Dose of Antiseizure Medications: A Model-Informed Individual Remedial Dosing.Neurology · 2023Article
- Modeling the protein binding non-linearity in population pharmacokinetic model of valproic acid in children with epilepsy: a systematic evaluation study.Frontiers in pharmacology · 2023Article
- Joint use of population pharmacokinetics and machine learning for optimizing antiepileptic treatment in pediatric population.Therapeutic advances in drug safety · 2023Article
- Developmental Population Pharmacokinetics-Pharmacodynamics of Meropenem in Chinese Neonates and Young Infants: Dosing Recommendations for Late-Onset Sepsis.Children (Basel, Switzerland) · 2022Article
- Population pharmacokinetic analysis of dexmedetomidine in children using real-world data from electronic health records and remnant specimens.British journal of clinical pharmacology · 2022Article
- Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients.Pharmaceutics · 2022Article
- Pharmacogenetics-based population pharmacokinetic analysis and dose optimization of valproic acid in Chinese southern children with epilepsy: Effect ofFrontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
9 authors.
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Abstract
BACKGROUND AND
objectiveValproic acid (VPA) follows a non-linear pharmacokinetic profile in terms of protein-binding saturation. The total daily dose regarding VPA clearance is a simple power function, which may partially explain the non-linearity of the pharmacokinetic profile; however, it may be confounded by the therapeutic drug monitoring effect. The aim of this study was to develop a population pharmacokinetic model for VPA based on protein-binding saturation in pediatric patients with epilepsy.
methodsA total of 1,107 VPA serum trough concentrations at steady state were collected from 902 epileptic pediatric patients aged from 3 weeks to 14 years at three hospitals. The population pharmacokinetic model was developed using NONMEM(®) software. The ability of three candidate models (the simple power exponent model, the dose-dependent maximum effect [DDE] model, and the protein-binding model) to describe the non-linear pharmacokinetic profile of VPA was investigated, and potential covariates were screened using a stepwise approach. Bootstrap, normalized prediction distribution errors and external evaluations from two independent studies were performed to determine the stability and predictive performance of the candidate models.
resultsThe age-dependent exponent model described the effects of body weight and age on the clearance well. Co-medication with carbamazepine was identified as a significant covariate. The DDE model best fitted the aim of this study, although there were no obvious differences in the predictive performances. The condition number was less than 500, and the precision of the parameter estimates was less than 30 %, indicating stability and validity of the final model.
conclusionThe DDE model successfully described the non-linear pharmacokinetics of VPA. Furthermore, the proposed population pharmacokinetic model of VPA can be used to design rational dosage regimens to achieve desirable serum concentrations.
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