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Concentration of metabolites of valproic acid in plasma of epileptic patients
Authors:W. L  scher
Affiliation:Laboratory of Pharmacology and Toxicology, Free University of Berlin, School of Veterinary Medicine, Berlin, Federal Republic of Germany
Abstract:With the help of synthetic reference substances, five metabolites of valproic acid (VPA) could be quantitated by gas chromatography in the plasma of 26 epileptic patients undergoing chronic therapy with sodium valproate. The products of beta-oxidation, i.e., 2-en-VPA, 3-hydroxy-VPA, and 3-keto-VPA were found to be the major metabolites of VPA in plasma, whereas the intermediates of omega-oxidation, 4-hydroxy-VPA and 5-hydroxy-VPA, were present only in markedly lower concentrations. It was thus confirmed that in addition to the excretion of VPA as the glucuronide, beta-oxidation is the preferred metabolic pathway of VPA in man. However, taking the anticonvulsant activity of the metabolites as derived from animal experiments into consideration, none of the metabolites found in human plasma seems to contribute markedly to the therapeutic effect of VPA. Thus, in most patients, VPA seems responsible for more than 90% of the antiepileptic activity during continued medication in man.
Keywords:Valproic acid    Metabolites    Plasma concentrations    Epileptic patients
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