ROLE OF ANTICONVULSANT THERAPEUTIC DRUG MONITORING IN IMPROVING CLINICAL OUTCOMES: AN EXAMPLE OF 12 ADULT EPILEPSY PATIENTS

1 , Jasmina Milovanovic 2 , Snežana V Jankovic 2 , Natalija Todorovic 3 , Nemanja Rancic 4 , Nikola Jestrovic 5 , 6 , Slobodan Jankovic 2 , Mihajlo Jakovljevic 2 1 Centar za radiolosku dijagnostiku , Klinicki centar Kragujevac, Srbija 2 Odsek za farmakologiju I toksikologiju, Fakultet medicinskih nauka, Kragujevac, Srbija 3 Klinika za neurologiju, Klinicki centar Kragujevac, Srbija 4 Fakultet medicinskih nauka, Univerzitet u Kreagujevcu, Srbija 5 Merck Sharp & Dohme Idea Inc., AG Beograd, Srbija 6 Farmaceutski fakultet, Univerzitet u Ljubljani, Slovenija Epilepsy, one of the most common neurological dis- eases, demands persistent and long-term therapy. In spite of the available therapeutic interventions for seizure dis- orders, the incidence of epilepsy and mortality associated with "status epilepticus" remain significant (1). The goal of seizure management is satisfying seizure control with minimal side effects (2). Quality of life (QoL) studies have suggested that patients who suffer even a single seizure per year exhibit significantly reduced QoL (3). Among the wide range of medications offered in the market, valproic acid is still considered by many to be "a gold standard" to treat many convulsive disorders, including absence , gen- eralised tonic-clonic seizures, myoclonic juvenile seizures, and photosensitive seizures . It also exhibits an acceptable toxicity profile compared with other anticonvulsants (4). The Serbian health care system is still not capable of sys- temic therapeutic drug monitoring in clinical practice. The underlying reasons are typical for an upper-middle income transitional market and are attributed to both financial con- straints and the lack of skilled, highly educated human re- source availability in the field. These reasons influenced the authors to report pilot trial results to provide a small move forward on the issue among local clinicians (5). The core aim of the trial presented was an exploration of the dose-response relationship in a small group of twelve adults suffering from epilepsy. The authors studied fre- quencies of drug adverse effects associated with long-term monotherapy and evaluated the appropriateness and clini- cal value of regular therapeutic drug monitoring (TDM) of valproic acid. The presence of a correlation between drug plasma concentration as an independent variable and fre- quency of seizures, frequency of adverse events and over- all life quality as dependent variables was also tested. The reported results are an unpublished fragment originating from a large-scale collaborative project on pharmacoki- netic modelling in juvenile epilepsy treatment (3-6).