Evaluation of Sodium Valproate Levels in Malnourished Childhood Epilepsy and Its Consequences

Abstract

Objectives. To measure and compare free fraction of serum levels of VPA (valproic acid) between non-malnourished and malnourished epileptic children and to evaluate the adverse effects (myopathy, hepatotoxicity). Material and methods. It is a prospective comparative observational case control study in which forty epileptic children (malnourished: 18 male/8 female, age 8.3±2.5, non-malnourished: 8 male/6 female, age 8.1±2.1) who fulfilled the inclusion criteria were recruited as study group and twenty children as control group (12male/8 female, age 6.0±2.8). Outcome measures monitored are serum VPA levels (total and free fraction of serum VPA), serum CK (creatinine kinase), SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic-transaminase). Using screening tool for the assessment of malnutrition in pediatrics (STAMP©), subjects are categorized into mild, moderate, severe malnourished as -1SD, -2SD, -3SD respectively Outcomes. There is an elevation in mean free fraction of VPA is 17.3±6.4 μg/ml whereas in non-malnourished group it was found to be 8.7±4.2 μg/ml with P= <0.001. While mean total drug concentration in malnourished and non-malnourished was found to be 88.6±49.9 μg/ml, 70.8±33.9 μg/ml respectively. Mean CK, SGOT, SGPT in control is 29.3±9.9IU/L, 28.5±5.4 IU/L,24.5±4.2 IU/L respectively. whereas mean CK, SGOT, SGPT in malnourished subjects is 16.9±9.1 IU/L, 28.8±8.5 IU/L,25.9±9.1 IU/L Correspondingly .while Mean CK, SGOT, SGPT in non-malnourished individuals is 15.7±11.3 IU/L,32.4±8.8 IU/L, 28.7±7.8 IU/L respectively. No correlation was observed between elevated serum drug concentrations, clinical response and side effects. Conclusion. We observed that clinical response and side effects are serum concentration independent hence our research make unnecessary to monitor serum drug concentration for every individual and drug monitoring should be restricted to subjects with severe ADR’s. Our data also suggest Valproate unveiled mitochondrial myopathy is limited to subgroup of population.

The Evaluation of Anti-Epileptic Drugs Dosage in Malnourished Children: Cases in Indonesian Community of Epilepsy

“…Previous research found that some patients need VA trough concentrations greater than 50-100mg/L to reduce 50% seizure frequency (Ghodke-Puranik et al, 2013;Methaneethorn, 2018). The free serum drug concentrations and clinical response in malnourished children was uncorrelated same as previous report study (Gampala et al, 2017). Severity of illness, comorbidities, history of illness, adverse drug reaction, adherence, and nutritional status were considered factors of clinical outcomes.…”

“…Variability of VA concentrations could be affected by pharmacokinetics and pharmacodynamics factors included polymorphism, gender, ages, protein binding, dosage form, malnutrition, and drug interactions (Marvanova, 2016;Methaneethorn, 2018). The patients with poor nutritional status need to be monitored individually on AEDs use, especially patients who show symptoms of severe drug side effects (Gampala et al, 2017). Even patients who treated with VA and PB were reported the risk of bone disease and micronutrients deficiency (Soltani et al, 2016).…”

“…Role of protein-energy, micronutrient deficiency, immunodeficiency, diet, drug therapy, drug-resistant epilepsy, and socio-cultural burden in developing countries were possible reasons of malnutrition and epilepsy were interrelated (Crepin et al, 2009). The study of 40 patients at an Indian hospital showed an increase in the concentration of the free drug sodium valproate in malnourished children compared to children with good nutritional status (Gampala et al, 2017). The pharmacological therapy using antiepileptic drugs has not been fully effective in overcoming seizures, where most antiepileptic drugs belong to a class of drugs with a narrow therapeutic index so that the therapeutic response is difficult to predict, especially in pediatric patients with poor nutritional status which could affect the effectiveness of therapy.…”