Evidence map›Paper›PMID 41918123›Full record

ArticleJournal of translational medicine2026

Monitoring of dual-drug combination therapy in pediatric epilepsy patients: a machine learning model for simultaneous VPA-LEV concentration-dose prediction.

Yue-Wen Chen, Si Chen, Yi-Wei Xie, He Zou, Xin Rao, Jian-Wen Xu, Wei Wu, Zhou-Jie Liu

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Article in Journal of translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Yue-Wen Chen *Department of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Si Chen *Department of Infectious Disease, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Yi-Wei XieDepartment of Pharmacy, Fuzhou First General Hospital, Fuzhou, China.
He ZouDepartment of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Xin RaoDepartment of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Jian-Wen XuDepartment of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
Wei WuDepartment of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China. wuwei@fjmu.edu.cn.
Zhou-Jie LiuDepartment of Pharmacy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China. liuzhoujie_08@163.com.ORCID http://orcid.org/0000-0003-3491-8859

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTo better meet the therapeutic demand in pediatric epilepsy patients (PEPs) receiving combined valproic acid (VPA) and levetiracetam (LEV) (therapeutic ranges: VPA 50–100 μg/mL; LEV 6–20 μg/mL.), We developed a dual-predictive machine learning (ML) model that integrates concentration monitoring with dose recommendation capabilities, serving as an adjunct tool for therapeutic drug monitoring (TDM).

methodsA retrospectively collected dataset comprising 497 paired concentration samples from 402 PEPs was used to train (i) classification models that predict adequacy of VPA and LEV concentrations and (ii) regression models that recommend individualised daily doses. Model explainability was interrogated with SHapley Additive exPlanations (SHAP) analysis to delineate concentration-dose covariates.

resultsAmong nine nonlinear ML algorithms, the Extra-Trees classifier achieved optimal performance for concentration adequacy prediction, delivering test-set accuracies and AUCs of 0.74 and 0.75 for VPA, and 0.75 and 0.75 for LEV, respectively. SHAP analysis elucidated body weight-normalized daily dose, blood urea nitrogen/creatinine (BUN/CREA) ratio, and platelet count (PLT) were identified as shared critical covariates. Serum uric acid (UA) exhibited LEV-specific positive regulation (SHAP rank 2, contribution 16.2%). For dose recommendation, an XGBoost multi-output regressor yielded test-set R2 values of 0.60 for both VPA and LEV daily dose. Body weight dominated dose predictions (VPA 70.2%; LEV 62.8%), followed by respective trough concentrations (VPA 7.1%; LEV 14.7%).

conclusionThis dual-prediction model enables simultaneous concentration monitoring and dose recommendation of VPA and LEV, offering a data-driven decision-support tool for personalised therapy in PEPs.

Indexed as

Drug MonitoringEpilepsyLevetiracetamMachine LearningValproic AcidAdolescentChildChild, PreschoolClassification AlgorithmsDose-Response Relationship, DrugDrug Therapy, CombinationFemaleHumansMalePrediction AlgorithmsPredictive Learning ModelsLevetiracetamValproic AcidLevetiracetamMachine learningPediatric epilepsy patientsSHAPValproic acid

Identifiers

PMID41918123
PMCPMC13154482

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.