Therapeutic Drug Monitoring of Valproic Acid in Patients with Monotherapy at Steady State

Document Type: Original Article


1 Department of Neurology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Pharmacodinamy & Toxicology, Pharmaceutical Research Center & School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Medicinal Chemistry, Pharmaceutical Research Center & School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Psychiatry, Faculty of Medicine, Psychiatric Research Center, Ebn-sina Hospital, Mashhad University of Medical Sciences, Mashhad, Iran


The role of therapeutic drug monitoring (TDM) in patient care has grown rapidly since its introduction three decades ago. The aim of present study was to evaluate the possible relationship between serum levels and the clinical response of valproic acid (VPA).
Materials and Methods
In the present study we evaluated a homogeneous group of adult patients receiving VPA monotherapy. A total of 18 epileptic patients who fulfilled inclusion and exclusion criteria were entered this prospective study. Steady state trough plasma concentration was determined by fluorescence polarization immunoassay (FPIA). The correlation between therapeutic response and VPA serum concentration was evaluated.
Mean VPA dose and mean total VPA plasma concentrations were 8.35±1.49 mg/kg/day and 50.40±4.18 pg/ml respectively. Mean VPA clearance was 8.84±4.43 (ml/kg/h). Plasma levels within the therapeutic range were found in 33% of epileptic patients. Plasma levels were below the therapeutic range in 67% of study population. Of patients 75% and 17% with sub-therapeutic levels achieved complete control and partial control respectively.
Poor correlation was found between the plasma concentration of VPA and its therapeutic effects. Therefore, this study showed that TDM of VPA will be useful only when individuals are non-responsive to treatment or vulnerable to adverse reactions with standard doses.


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