Does steady state serum level of Valproic acid correlate with dose, seizure response and frequency of adverse drug reactions in Pakistani children with epilepsy?

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Epilepsy is a heterogeneous disorder and its treatment is often complicated by variable drug response. Antiepileptic properties of Valproic acid were discovered in 1963 and since then it is widely used for treatment of epilepsy. The objective of this study was to explore the correlation of steady state serum level of Valproic acid with dose, seizure response and frequency of adverse drug reactions in Pakistani children with epilepsy. This prospective analytical study was conducted in the Neurology Department-The Children Hospital and The Institute of Child Health Multan, Pakistan from March 2009 to February 2010. Sixty children between one to 14 years of age taking Valproic acid for treatment of epilepsy, for more than 3 months as monotherapy were included. Age, sex, dose of Valproic acid, type of seizure, response of seizure with treatment and any side effect of drug were noted. Trough Valproic acid serum level was measured by Latex Enhanced Immunoturbidometric Method by Randox VPA 1×Series Kit according to manufacturer instructions. Chi square test was used to measure the relationship of serum level with dose, seizure response and frequency of adverse drug reactions. P value of less than 0.05 was considered as significant. Our results showed that male female ratio was 1.1:1. Mean age was 7.3 ± 3.9 yr. Mean dose of Valproic acid was 32.4 ± 11.3 mg/kg/day. Generalized tonic clonic seizures were noted in 50% of patients, complex partial in 16.7%, myoclonic in 15%, absence seizures in 5% and mixed type of seizures was noted in 8.3% of patients. Complete seizure response was noted in 60% of patients, partial response in 18.3% and no response in 21.7% of patients. Serum level of 50–100 μg/mL (therapeutic) was noted in 38.30% of patients, below 50 μg/mL (subtherapeutic) in 46.8% and above 100 μg/mL (supratherapeutic) in 14.9% of patients. Serum level below 50 μg/mL was noted in 60.7% of children with complete seizure response while 50–100 μg/mL was noted in 21.7% of children with no response. Adverse drug reactions were noted in 66.6% of patients in this study. These adverse reactions were noted in 64.2% of children with serum level below 50 μg/mL, 65.2% with 50–100 μg/mL and 77.7% with serum level above 100 μg/mL. No correlation of Valproic acid serum level was noted with dose (P value 0.546), seizure response (P value 0.998) and frequency of adverse drug reactions (P value 0.743) in this study. No significant correlation of Valproic acid serum level was noted with dose, seizure response and frequency of majority of adverse drug reactions.