Chulalongkorn Medical Journal


Objectives : To determine whether there are valproic acid (VPA) pharmacokinetic (PK)parameters differences between the VPA-responsive and VPA-resistantpatient groups.Methods : Thirty-three subjects (14 patients were in VPA-resistant group and 19patients in VPA-responsive group) who were epileptic patients were recruitedfrom the Neurology Clinic, Neurology Institute, Bangkok. Their ages were15 - 65 years old. They were either treated with VPA (Depakine Chrono)monotherapy or polytherapy in which the combined drug did not havethe same metabolic pathways as VPA. At steady state condition, two bloodsamples were collected from the subjects during elimination phase,approximately five hours apart. Individual PK parameter values of VPAwere estimated using the equations for a linear one-compartment modelwith a first-order declining of drug concentration after the end of 14 hourszero-order drug release. Chi-square test and the odds ratio were used toanalize the data.Results : Under steady state condition after consuming Depakine Chrono®, avolume of distribution value (Vd) obtained from total VPA concentrationswas statistically significantly different between two patient groups (p<0.05).Additionally, Vd value of total VPA less than 0.3 l/kg was associated withnonresponsive to VPA treatment (p<0.05). While, half life (t ½ ) of totalVPA less than 25 hours and parameters obtained from unbound VPAconcentrations such as Vd value less than 0.7 l/kg and t½ less than10 hours had higher tendency to belong to the VPA-resistant group butthey did not reach statistical significance (p>0.05); however, all theseparameters were taken significant when p <0.1.Conclusions : The PK parameter values estimated from two blood samples collectedduring the routine clinical therapeutic drug monitoring might be used toidentify whether or not the epileptic patient responds to the VPA therapyand thus could reduce the steps of trial and error.


Faculty of Medicine, Chulalongkorn University

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