Relationship between serum concentration and dose of valproic acid during monotherapy in adult outpatients.

Abstract

The relationship between serum concentration and dose of valproic acid (VPA) is reported to be variable and inconsistent. However, studies evaluating this relationship have included individuals of varying ages and patients receiving potentially interacting medications. In this study, the relationship between VPA serum concentration and dose was evaluated in a homogeneous patient population. Medical records of 60 adult outpatients with epilepsy receiving VPA monotherapy were examined retrospectively for VPA dose (milligrams per kilogram) and corresponding serum VPA concentrations. A significant linear correlation was found in the relationship between VPA dose and serum concentration among all patients (r = 0.63; p less than 0.01). However, considerable interindividual variability in this ratio was demonstrated [coefficient of variation (CV) = 28.9%], and the ratio was significantly dependent on VPA dose. In three selected individual patients, a significant linear correlation was also demonstrated in the VPA serum concentration:dose relationship over time (r = 0.91, 0.94, 0.96; p less than 0.05 for all three patients) with substantially less variability (CV = 10.2-14.6%) and without significant dose dependency, suggesting that this parameter may be useful for guiding VPA dosage adjustment and monitoring patient compliance. Further study is required to evaluate the utility of the serum concentration:dose ratio in monitoring VPA therapy.