Frontiers in pharmacology · 2026
Optimization of individualized therapy with oral valproic acid in pediatric patients with epilepsy based on factors influencing blood concentrations.
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Qin Yinhui, Zhang Na, Zhang Panpan, Teng Yuetai, Xia Zhengchao, Mao Zhenkun, Wang Lei, Yang Yan, Niu Weihong
Аннотация
BACKGROUND: Valproic acid (VPA) is widely used in pediatric epilepsy, but its blood concentrations vary considerably among pediatric patients with epilepsy. This study aimed to investigate the factors influencing VPA blood concentrations in this population.
METHODS: This study included patients with epilepsy aged 0-18 years who were treated with VPA. Clinical data collected included age, gender, daily dose, biochemical parameters (liver and renal function), and electrolyte levels. VPA blood concentrations were measured by immunoassay. Correlation analyses and linear regressions were conducted to assess associations between clinical variables and VPA blood concentrations.
RESULTS: The mean VPA blood concentration was 69.82 ± 25.22 μg/mL, and 70.06% of patients had blood concentrations within the therapeutic range. Daily dose was positively correlated with blood concentration (r = 0.319, P < 0.001). Age was significantly associated with VPA blood concentration, with younger children (<6 years) receiving lower daily doses and exhibiting lower blood concentrations than older age groups (both P < 0.001). Creatinine and globulin levels were positively correlated with VPA blood concentrations (all P < 0.001), whereas alanine aminotransferase levels showed a negative correlation with blood concentrations (P < 0.001). Notably, calcium and phosphorus levels were negatively correlated with VPA blood concentrations.
CONCLUSION: VPA blood concentrations in the study population were influenced by multiple factors, including daily dose, age, renal and hepatic function, and electrolyte status. Given the marked inter-individual variability, individualized treatment guided by therapeutic drug monitoring (TDM) is essential for optimizing dosing accuracy and therapeutic efficacy.
METHODS: This study included patients with epilepsy aged 0-18 years who were treated with VPA. Clinical data collected included age, gender, daily dose, biochemical parameters (liver and renal function), and electrolyte levels. VPA blood concentrations were measured by immunoassay. Correlation analyses and linear regressions were conducted to assess associations between clinical variables and VPA blood concentrations.
RESULTS: The mean VPA blood concentration was 69.82 ± 25.22 μg/mL, and 70.06% of patients had blood concentrations within the therapeutic range. Daily dose was positively correlated with blood concentration (r = 0.319, P < 0.001). Age was significantly associated with VPA blood concentration, with younger children (<6 years) receiving lower daily doses and exhibiting lower blood concentrations than older age groups (both P < 0.001). Creatinine and globulin levels were positively correlated with VPA blood concentrations (all P < 0.001), whereas alanine aminotransferase levels showed a negative correlation with blood concentrations (P < 0.001). Notably, calcium and phosphorus levels were negatively correlated with VPA blood concentrations.
CONCLUSION: VPA blood concentrations in the study population were influenced by multiple factors, including daily dose, age, renal and hepatic function, and electrolyte status. Given the marked inter-individual variability, individualized treatment guided by therapeutic drug monitoring (TDM) is essential for optimizing dosing accuracy and therapeutic efficacy.