Risk Factors and Multiple Interaction Effects for Hyperammonemia in Patients Receiving Valproic Acid

IF 2.1 4区医学 Q3 PHARMACOLOGY & PHARMACY

Fundamental & Clinical Pharmacology Pub Date : 2025-06-22 DOI:10.1111/fcp.70030

Chien-Chou Su, Tsai-Kuei Huang, Ching-Sen Shih, Yi-Chia Su

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引用次数: 0

Abstract

Background

Valproic acid (VPA) use is associated with an increased risk of hyperammonemia (HA); however, the specific interactions between HA risk factors in VPA-treated patients remain unclear.

Objectives

This study aimed to identify and assess the effects of multiple interactions between different risk factors affecting HA to improve clinical risk stratification in patients undergoing VPA therapy.

Methods

We conducted a retrospective cohort study by reviewing the medical records of patients treated with VPA at a single center from January 2019 to December 2021. The SHapley Additive exPlanations (SHAP) method was used to interpret model predictions, revealing the relative importance and interactions of factors affecting HA risk. SHAP interaction scores were used to assess the effects of multiple interactions between features, providing a comprehensive analysis of how risk factors interact.

Results

This study identified the Top 15 predictors of HA, ranked by importance: patient age, VPA blood concentration, VPA dose, epilepsy, VPA treatment duration, levetiracetam use, hypertension, mental disorders, and number of medications. Notable multiple interaction effects were observed, particularly between age and factors including VPA concentration, epilepsy, and treatment duration. Younger patients and those with elevated VPA concentrations were at increased risk of developing HA, especially when epilepsy or polypharmacy were present.

Conclusions

This study highlights several critical factors potentially influencing HA development in VPA-treated patients, particularly younger patients, those with epilepsy, or those undergoing polypharmacy. However, as a single-center retrospective study, these findings necessitate further validation through additional research.

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丙戊酸治疗患者高氨血症的危险因素及多重相互作用

背景丙戊酸（VPA）的使用与高氨血症（HA）的风险增加有关；然而，在vpa治疗的患者中，HA危险因素之间的具体相互作用尚不清楚。本研究旨在识别和评估影响HA的不同危险因素之间多重相互作用的影响，以改善VPA治疗患者的临床风险分层。方法通过回顾2019年1月至2021年12月在单一中心接受VPA治疗的患者的病历，进行回顾性队列研究。使用SHapley加性解释（SHAP）方法解释模型预测，揭示影响HA风险的因素的相对重要性和相互作用。SHAP相互作用评分用于评估特征之间多重相互作用的影响，提供了对危险因素如何相互作用的全面分析。结果本研究确定了HA的前15个预测因素，按重要性排序：患者年龄、VPA血药浓度、VPA剂量、癫痫、VPA治疗时间、左乙西坦使用、高血压、精神障碍和药物数量。观察到明显的多重相互作用效应，特别是年龄与VPA浓度、癫痫和治疗时间等因素之间的相互作用。年轻患者和VPA浓度升高的患者发生HA的风险增加，特别是当癫痫或多药并存时。本研究强调了几个可能影响vpa治疗患者HA发展的关键因素，特别是年轻患者、癫痫患者或接受多种药物治疗的患者。然而，作为一项单中心回顾性研究，这些发现需要通过额外的研究进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fundamental & Clinical Pharmacology 医学-药学

CiteScore

5.30

自引率

6.90%

发文量

111

审稿时长

6-12 weeks

期刊介绍： Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.