Trial reportJournal of clinical pharmacology2012
Population pharmacokinetics of valproic acid in pediatric patients with epilepsy: considerations for dosing spinal muscular atrophy patients.
Trial report in Journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
What it found
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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
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- A systematic review of population pharmacokinetics of valproic acid.British journal of clinical pharmacology · 2018Pooled it
- Physiologically-Based Pharmacokinetic Modeling of Total and Unbound Valproic Acid to Evaluate Dosing in Children With and Without Hypoalbuminemia.Clinical pharmacokinetics · 2024Article
- Physiologically based mechanistic insight into differential risk of valproate hepatotoxicity between children and adults: A focus on ontogeny impact.CPT: pharmacometrics & systems pharmacology · 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
- Population Pharmacokinetics of Valproic Acid in Pediatric and Adult Caucasian Patients.Pharmaceutics · 2022Article
- Comparative pharmacokinetics of valproic acid among Pakistani and South Korean patients: A population pharmacokinetic study.PloS one · 2022Article
- Pharmacogenetics-based population pharmacokinetic analysis and dose optimization of valproic acid in Chinese southern children with epilepsy: Effect ofFrontiers in pharmacology · 2022Article
- Severe Pancytopenia Induced by Valproic Acid.Cureus · 2020Article
- Effect of CYP2C19, UGT1A8, and UGT2B7 on valproic acid clearance in children with epilepsy: a population pharmacokinetic model.European journal of clinical pharmacology · 2018Article
- A population pharmacokinetic model of valproic acid in pediatric patients with epilepsy: a non-linear pharmacokinetic model based on protein-binding saturation.Clinical pharmacokinetics · 2015Article
- Pharmacogenetics in clinical pediatrics: challenges and strategies.Personalized medicine · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Valproic acid (VPA) dosing strategies used in recent clinical trials in patients with spinal muscular atrophy (SMA) have utilized a paradigm of monitoring trough levels to estimate drug exposure with subsequent dose titration. The validity of this approach remains uncertain and could be improved by understanding sources of pharmacokinetic variability. A population pharmacokinetic analysis of VPA in pediatric patients with epilepsy was recently performed. The pooled data set included 52 subjects with epilepsy, ages 1 to 17 years, who received intravenous and/or various oral formulations. The data was best fit by a 2-compartment model; inclusion of age and weight reduced intersubject variability for clearance (41%), central volume (70%), and peripheral volume (42%) over the base model. The final model for clearance and volume parameters was clearance = 0.854 · (weight/70)(0.75); central volume of distribution = 10.3 · (weight/70)(1.0) · (age/8.5)(-0.267); peripheral volume of distribution = 4.08 · (weight/70)(1.0); and intercompartmental clearance = 5.34 · (weight/70)(0.75). Application of the model to data from a clinical trial in SMA patients suggests altered kinetics, perhaps based on underlying physiologic differences such as alterations in lean body mass. Future studies in SMA should incorporate modeling and simulation techniques to support individualized dosing and further assess if additional patient-specific factors necessitate alternative dosing strategies.
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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.