Comparative analysis of valproic acid concentrations in terms of dosing and clinical effect monitoring in different age patients with diagnosed epilepsy

Abstract

Subject of research Therapy drug monitoring under the control of valproic acid (VPA) is now a well-established tool for the treatment of epilepsy. The pharmacokinetic variability of VPA and inter-individual differences in epilepsy type/seizure severity depending on patients’ age determine serum concentration of this drug in an individual patient. The application of the "individual therapeutic concentration" may be a useful indicator taking into account the clinical condition of a patient. Aim. The aim was to compare values of stationary VPA concentrations in terms of dosing and clinical effect monitoring in different age of epileptic patients. Methods Thirty-three patients at age 20-70 years were divided into three groups: I 20-25 years (n = 15), II 26-39 years (n = 9), III 40-70 years (n = 9). Nine patients were treated with VPA in monotherapy, others received VPA with at least one antiepileptic drug (n = 24). Plasma VPA Cssmin were measured, at steady state, using the commercial CEDIA® Valproic Acid II Assay. Results VPA Cssmin values in groups I, II and III were within the therapeutic range: 93%, 56% and 30%; above it: 0%, 33% and 55% and below it: 6%, 22% and 0%, respectively. The percentage of patients with the least frequent seizure was highest in group I (60%) compared to II (54%) and III (44%). The highest frequency of seizures was in group III (25 seizures/week) compared to group I (6.5 seizures/week). The percentage of patients with 1 attack in 1-7 days was comparable in groups: I (13%), II (12%) and III (12%). On the other hand, the percentage of patients free from epileptic seizures (> 1 year) was the highest in group I (53%) compared to group II (44%) and III (22%). Conclusions The reasons for the obtained differences could be drug interactions, nutritional style and the lack of compliance. The unpredictable VPA dose-concentration-clinical effect supports the need to optimize the therapy and define "individual therapeutic concentration". Using it in practice along with patient’s individual indications and clinical condition allows to achieve seizure-free period with good tolerance or optimal seizure control with minimal VPA side-effects.

Keywords

• valproic acid
• therapeutic drug monitoring
• epilepsy
• clinical patient condition