Problems faced by valproic acid therapy in children

Valproic acid has been clinically applied as the first-line drug for epilepsy patients, and long-term practice has confirmed the clinical efficacy of this drug in treating epilepsy. However, this drug is susceptible to arrange of complications if not properly managed, with a particular concern being the negative impact on cognitive ability in children. Therefore,

personalized medication adjustment is often needed according to the therapeutic effect or the results of drug concentration detection (TDM), and the exact same standard treatment regimen should not be used for every patient. Several papers have been published exploring exactly what clinical or individual factors are influencing valproic acid blood concentrations. The majority of these studies have focused on the impact of various drug combinations on valproic acid pharmacokinetics ^{[1, 2]}. However, there has been a paucity of research analyzing the role of physiological factors. This study aims to address this gap by investigating the extent to which physiological factors affect pediatric patients and the importance of therapeutic drug monitoring (TDM) in their treatment.

Methodology and Results

Tables  1  Characterization of Group A/B

A total of 805 children between the ages of 2 and 18 years who participated in the study were treated with valproic acid and had at least 2 blood trough concentrations tested during the trial (C₀). Information was collected regarding the subjects’ age, gender, weight, frequency of onset, last date of onset, mode of administration, and drug concentratio. The children of subjects participating in the study were categorized into two groups, A (in range) and B (out of range), based on whether they were within the therapeutic range (TR) or not (C₀), and were compared in parallel.

The analysis revealed that age is a significant factor influencing valproic acid C₀ with a corresponding 3.79% increase in TR attainment for additional year of age. It is possible that a number of factors are involved in this process. Firstly, the metabolism of valproic acid in children is enhanced with age. Secondly, children's body weight varies with age, resulting in higher concentrations/doses in group A compared to group B due to corresponding dosage adjustments based on body weight. Thirdly, treatment adherence is better in older children than in younger children. Therefore, the age of the children should be considered in the optimization of the treatment regimen.

Another factor that has a significant impact on valproic acid C₀ is the number of TDM tests conducted. Previous studies have indicated that TDM is only employed when a patient is not responding to treatment or has experienced an adverse reaction to the standard dose. However, this study demonstrated that frequent TDM testing can facilitate the attainment of the standard dose of valproic acid C₀ more expeditiously (7.39% increase in odds), even in the context of pediatric patients who are responding to treatment.

Conclusion

Achieving valproic acid C₀ in pediatric patients will be more challenging due to the effects of weight changes, changes in metabolic function, etc. in children. The findings of this study indicate that age and frequency of TDM utilization are two key factors that exert a significant influence. It is therefore imperative that TDM be closely monitored in order to maintain stable control of valproic acid C₀ in the effective range.