Does steady state serum level of Valproic acid correlate with
dose, seizure response and frequency of adverse drug reactions in Pakistani
children with epilepsy?
Affiliations: Department of Pediatric Neurology, The Children
Hospital and The Institute of Child Health Multan, Multan, Pakistan | Department of Pediatrics, Nishtar Hospital Multan, Pakistan | Department of Pathology, The Children Hospital and The
Institute of Child Health Multan, Multan, Pakistan | Department of Pediatrics, The Children Hospital and
The Institute of Child Health Multan, Multan, Pakistan
Note: [] Correspondence: Dr. Nuzhat Noureen, Department of Pediatric
Neurology, The Children Hospital and The Institute of Child Health, Multan,
Multan, Pakistan. Tel.: +92 (0)3327409471; E-mail: [email protected]
Abstract: 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.
Keywords: Children, Valproic acid, drug level, epilepsy
