Factors Influencing Sodium Valproate Serum Concentrations in Patients with Epilepsy Based on Logistic Regression Analysis

Abstract

Background We aimed to explore the risk factors that affect the serum concentration of sodium valproate (VPA-Na) in patients with epilepsy and to provide references for the rationale of the use of VPA-Na. Material/Methods The enzyme-multiplied immunoassay technique was used to determine the serum VPA-NA concentrations of 109 patients, and the results were retrospectively analyzed and summarized. A multivariate logistic regression model was used to analyze substandard serum VPA-Na concentrations. Results Fifty-six patients (51.38%) treated with VPA-Na tablets were within the effective treatment range of 50–100 μg/mL, while 53 patients (48.62%) were out of the treatment range. The results indicated that the standard-reaching rate of serum drug concentration in the juvenile group was higher than that in the adult and elderly groups; the standard-reaching rates of serum drug concentrations in the low-dose group and the intermediate-dose group were lower than that in the high-dose group; and the standard-reaching rate of serum drug concentration in the group receiving carbapenems in combination was lower than that in the non-combination group; all differences were statistically significant. The combination with carbapenems and enzyme inducers was an independent risk factor for VPA-Na serum concentration below the target level in hospitalized patients. Conclusions To improve clinical efficacy and reduce the occurrence of adverse reactions, there is a need for therapeutic drug monitoring of VPA-Na. Moreover, individual administration should be implemented when VPA-Na tablets are used in the treatment of epilepsy because of the significant fluctuation in VPA-Na blood concentration.

Serum concentrations of valproic acid in people with epilepsy: Clinical implication

“…The concentration of valproic acid in serum has been evaluated, observing that they are within the therapeutic range; for this study, values of 50-100 mg/L recommended by existing guidelines were considered (Lan et al, 2021;Patsalos et al, 2018). The value of the Mann-Whitney U Test for the median serum concentrations (p = 0.952 α>0.05) was not different between the male and female sex groups.…”

“…Therapeutic drug monitoring (TDM) of VPA is justified by the three-compartment pharmacokinetic model, protein binding and saturable metabolism (Shaikh et al, 2018;Taylor et al, 2019), enzymes expressed by genes that present allelic variants (Alvarado et al al., 2019), due to age, sex, nonpersonalized doses (Buoli et al, 2018) and due to pharmacological interactions (Hernández-Ramos et al, 2021) that generate unpredictable serum levels, and whose clinical implication is significant (Alvarado et al, 2020;Cotuá et al, 2017). With the values of the serum concentration of the drug, it is interpreted if the drug is within the therapeutic index to control the symptoms of epilepsy (Shaikh et al, 2018); when the drug does not reach the minimum effective concentration (CmE), the symptoms of epilepsy are not adequately controlled, and pharmacological treatment is likely to fail (Lan et al, 2021), and when the free drug exceeds the minimum toxic concentration (CMT) predisposes to hepatic, hematological, neuro-logical toxicity and metabolic syndrome (Carmona-Vázquez et al, 2015;Lan et al, 2021). As there are subtherapeutic and supratherapeutic levels, the level/dose index is determined to adjust and individualize the dose for each patient; additionally, through pharmacotherapeutic follow-up, side effects, toxicity, and non-compliance with pharmacological therapy are detected (Alvarado et al, 2020;Canisius et al, 2020;Cotuá et al, 2017).…”

Development and Internal Validation of Machine Learning Algorithms for Determining Sodium Valproate Concentrations below the Standard Level Using a Risk Prediction Model of Children with Epilepsy

“…Low blood concentrations of sodium valproate indicate limited ability to control the disease, and high blood concentrations can easily lead to intellectual disability or memory impairment in children. Terefore, monitoring the blood concentration of sodium valproate is an efective method to ensure curative efects and safety and realize individualized treatment [5]. Terefore, this study adopted a retrospective analysis method to collect and analyze the results of the monitoring of the serum concentration of sodium valproate in children with epilepsy in our hospital and used a machine learning method to analyze the relationship between age, sex, dosage form, experimental examination indices, and blood concentration to provide a reference for the rational clinical application of sodium valproate in children with epilepsy.…”