Studies on the pharmacokinetics of total and free valproate in mono- and bitherapy with carbamazepine in epileptic children and adolescents

The aim of this study was to obtain a pharmacokinetic calculation for valproic acid (VPA) and its free fraction in 50 children and adolescents (4-18 years) treated for epilepsy in VPA monotherapy and bitherapy with carbamazepine (CBZ). The diurnal fluctuation of serum concentration of total and free VPA during monotherapy was observed. The additional antiepileptic medication of VPA and CBZ was connected with prominent diurnal free VPA serum fluctuations. Pharmacokinetic parameters of total and free VPA in monotherapy were significantly different. The change of free and total VPA pharmacokinetics during bitherapy with CBZ was observed, too. No changes in half-life time of VPA in mono- and bitherapy were noticed. The variability of pharmacokinetic parameters of free VPA suggests the need for monitoring unbound VPA plasma concentrations during bitherapy with CBZ.