ArticleBritish journal of clinical pharmacology2018
Pharmacokinetic interactions and dosing rationale for antiepileptic drugs in adults and children.
Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Investigation of the Roles of New Antiepileptic Drugs and Serum BDNF Levels in Efficacy and Safety Monitoring and Quality of Life: A Clinical Research.Current clinical pharmacology · 2020Trial
- Prediction of Zonisamide Concentration in Pediatric Patients With Epilepsy: A Machine Learning Approach.CNS neuroscience & therapeutics · 2026Article
- Delayed gastric emptying and antiseizure medication absorption: a potential pharmacokinetic consideration for GLP-1/GIP receptor agonists.European journal of clinical pharmacology · 2026Article
- Association BetweenPharmaceuticals (Basel, Switzerland) · 2025Article
- A Comparison of AI and Population PK Models to Predict the Concentrations of Antiepileptic Drugs Using Therapeutic Drug Monitoring Records.Clinical and translational science · 2025Article
- Population pharmacokinetics of oxcarbazepine 10-monohydroxy derivative in Chinese adult epileptic patients.European journal of hospital pharmacy : science and practice · 2023Article
- Formulation and Characterisation of Carbamazepine Orodispersible 3D-Printed Mini-Tablets for Paediatric Use.Pharmaceutics · 2023Article
- Loss of normal Alzheimer's disease-associated Presenilin 2 function alters antiseizure medicine potency and tolerability in the 6-Hz focal seizure model.Frontiers in neurology · 2023Article
- Effect of cenobamate on the single-dose pharmacokinetics of multiple cytochrome P450 probes using a cocktail approach in healthy subjects.Clinical and translational science · 2022Article
- Anticonvulsant Effectiveness and Neurotoxicity Profile of 4-butyl-5-[(4-chloro-2-methylphenoxy)methyl]-2,4-dihydro-3H-1,2,4-triazole-3-thione (TPL-16) in Mice.Neurochemical research · 2021Article
- Clinical trial simulations of the interaction between cannabidiol and clobazam and effect on drop-seizure frequency.British journal of clinical pharmacology · 2020Article
- Persistent Hypersomnolence Following Clobazam in a Child With Epilepsy and Undiagnosed CYP2C19 Polymorphism.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2020Article
- Effectiveness and Safety/Tolerability of Eslicarbazepine Acetate in Epilepsy Patients Aged ≥ 60 Versus < 60 Years: A Subanalysis from the Euro-Esli Study.Neurology and therapy · 2019Article
- Effect of Age-Related Factors on the Pharmacokinetics of Lamotrigine and Potential Implications for Maintenance Dose Optimisation in Future Clinical Trials.Clinical pharmacokinetics · 2018Article
- Pharmacokinetic interactions and dosing rationale for antiepileptic drugs in adults and children.British journal of clinical pharmacology · 2018Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsPopulation pharmacokinetic modelling has been widely used across many therapeutic areas to identify sources of variability, which are incorporated into models as covariate factors. Despite numerous publications on pharmacokinetic drug-drug interactions (DDIs) between antiepileptic drugs (AEDs), such data are not used to support the dose rationale for polytherapy in the treatment of epileptic seizures. Here we assess the impact of DDIs on plasma concentrations and evaluate the need for AED dose adjustment.
methodsModels describing the pharmacokinetics of carbamazepine, clobazam, clonazepam, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, topiramate, valproic acid and zonisamide in adult and paediatric patients were collected from the published literature and implemented in NONMEM v7.2. Taking current clinical practice into account, we explore simulation scenarios to characterize AED exposure in virtual patients receiving mono- and polytherapy. Steady-state, maximum and minimum concentrations were selected as parameters of interest for this analysis.
resultsOur simulations show that DDIs can cause major changes in AED concentrations both in adults and children. When more than one AED is used, even larger changes are observed in the concentrations of the primary drug, leading to significant differences in steady-state concentration between mono- and polytherapy for most AEDs. These results suggest that currently recommended dosing algorithms and titration procedures do not ensure attainment of appropriate therapeutic concentrations.
conclusionsThe effect of DDIs on AED exposure cannot be overlooked. Clinical guidelines must consider such covariate effects and ensure appropriate dosing recommendations for adult and paediatric patients who require combination therapy.
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