ArticleCPT: pharmacometrics & systems pharmacology2022
Physiologically-based pharmacokinetic modeling of oxcarbazepine and levetiracetam during adjunctive antiepileptic therapy in children and adolescents.
Article in CPT: pharmacometrics & systems pharmacology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Physiologically Based Pharmacokinetic Modeling of Oxcarbazepine to Characterize Its Disposition in Children with Obesity.Journal of clinical pharmacology · 2026Article
- Utilizing Minimal Physiologically Based Pharmacokinetic Modeling to Bridge Bevacizumab Pharmacokinetics from Adult to Pediatric Patients.The AAPS journal · 2025Article
- A Physiologically Based Modeling Approach to Evaluate Intravenous Levetiracetam Dosing in Term and Preterm Neonates.Journal of clinical pharmacology · 2025Article
- Pharmacokinetics and Pharmacodynamics of Levetiracetam in Neonatal Seizures: What We Still Need to Know.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Physiologically-based pharmacokinetic modeling and simulation for initial dose optimization of levetiracetam in pediatrics.Frontiers in pharmacology · 2025Article
- Comparison of oxcarbazepine metabolite concentrations measured by EMIT-based Siemens Viva-ProEFrontiers in pharmacology · 2025Article
- Utilizing Physiologically Based Pharmacokinetic Models to Support Rational Medication in Chinese Elderly Population.Drug design, development and therapy · 2025Article
- Coupling Pre- and Postnatal Infant Exposures with Physiologically Based Pharmacokinetic Modeling to Predict Cumulative Maternal Levetiracetam Exposure During Breastfeeding.Clinical pharmacokinetics · 2024Article
- Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population.Clinical pharmacokinetics · 2024Article
- Sources of pharmacokinetic and pharmacodynamic variability and clinical pharmacology studies of antiseizure medications in the pediatric population.Clinical and translational science · 2024Review
- Revisiting the concept of drug-resistant epilepsy: A TASK1 report of the ILAE/AES Joint Translational Task Force.Epilepsia · 2023Article
- Physiologically based pharmacokinetic modeling of levetiracetam to predict the exposure in hepatic and renal impairment and elderly populations.CPT: pharmacometrics & systems pharmacology · 2023Article
- Joint use of population pharmacokinetics and machine learning for optimizing antiepileptic treatment in pediatric population.Therapeutic advances in drug safety · 2023Article
- Application of Physiologically Based Pharmacokinetic Modeling to Predict Maternal Pharmacokinetics and Fetal Exposure to Oxcarbazepine.Pharmaceutics · 2022Article
- Physiologically-based pharmacokinetic modeling of oxcarbazepine and levetiracetam during adjunctive antiepileptic therapy in children and adolescents.CPT: pharmacometrics & systems pharmacology · 2022Article
- Development of a pediatric physiologically-based pharmacokinetic model to support recommended dosing of atezolizumab in children with solid tumors.Frontiers in pharmacology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Oxcarbazepine (OXZ) and levetiracetam (LEV) are two new generation anti-epileptic drugs, often co-administered in children with enzyme-inducing antiepileptic drugs (EIAEDs). The anti-epileptic effect of OXZ and LEV are linked to the exposure of OXZ's active metabolite 10-monohydroxy derivative (MHD) and (the parent) LEV, respectively. However, little is known about the confounding effect of age and EIAEDs on the pharmacokinetics (PKs) of MHD and LEV. To address this knowledge gap, physiologically-based pharmacokinetic (PBPK) modeling was performed in the PK-Sim software using literature data from children greater than or equal to 2 years of age. Age-related changes in clearance (CL) of MHD and LEV were characterized, both in the presence (group 1) and absence (group 2) of concomitant EIAEDs. The drug-drug interaction effect of EIAEDs was estimated as the difference in CL estimates between groups 1 and 2. PBPK modeling suggests that bodyweight normalized CL (ml/min/kg) is higher in younger children than their older counterparts (i.e., due to an influence of age). Concomitant EIAEDs further increase MHD's CL to a fixed extent of 25% at any age, but EIAEDs' effect on LEV's CL increases with age from 20% (at 2 years) to 30% (at adolescence). Simulations with the maximum recommended doses (MRDs) revealed that children between 2 and 4 years and greater than 4 years, who are not on EIAEDs, are at risk of exceeding the reference exposure range for OXZ and LEV, respectively. This analysis demonstrates the use of PBPK modeling in understanding the confounding effect of age and comedications on PKs in children and adolescents.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.