Lack of relationship between sodium valproate-induced adverse effects and the plasma concentration of its metabolite 2-propylpenten-4-oic acid

Summary The concentrations of valproic acid (VPA) and of its metabolites 3-oxo-VPA and 4-en-VPA were measured in the plasma of 12 selected epileptic patients 1,2,3, and 4 h after administration of a loading dose of VPA. Four of the patients, all on polytherapy, had had short-term adverse effects during chronic VPA treatment, and in them there has been abnormal NH₃-values after a test doese of VPA. Eight patients (4 on monotherapy and 4 on polytherapy) had been free from adverse effects. No significant difference in the VPA, 3-oxo-VPA and 4-en-VPA concentrations was found between the three groups of patients. Accumulation of 4-en-VPA is not involved in the short-term adverse effects and hyperammonaemia induced by VPA.