Plasma levels of valproic acid and its metabolites during continued treatment in dogs

Dogs were treated with the anti-epileptic drug valproic acid (VPA) for 2 weeks in order to determine whether therapeutic plasma levels could be maintained. VPA (as the sodium salt) was administered in a dosage of 170-180 mg/kg/day divided into three equal doses in the form of enteric-coated tablets. Due to the rapid elimination of this drug in dogs, therapeutic plasma levels were reached only intermittently. However, the concentrations maintained may be sufficient for anti-epileptic therapy in dogs because the lower plasma protein binding of VPA in this species gives rise to higher central concentrations compared with man. Furthermore, some VPA metabolites previously shown to exert anticonvulsant activity (2-en-VPA and 3-keto-VPA) were found in relatively high concentrations in dog plasma. We would recommend the dosages used in this study as a basis for assessment of VPA in the treatment of canine epilepsy.