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BioMed Research International
Volume 2014, Article ID 217269, 7 pages
Research Article

Hyperammonemia Associated with Valproic Acid Concentrations

1Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la República, Avenida General Flores 2124, P.O. Box 1157, 11800 Montevideo, Uruguay
2Therapeutic Drug Monitoring Service, “Dr. Manuel Quintela” Clinical Hospital, Universidad de la República, Avenida Italia s/n, 11609 Montevideo, Uruguay
3“Sanatorio Canzani” Hospital, Banco de Previsión Social, Martín García 1363, 11800 Montevideo, Uruguay

Received 10 February 2014; Revised 28 March 2014; Accepted 11 April 2014; Published 29 April 2014

Academic Editor: Slaven Erceg

Copyright © 2014 Marta Vázquez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Valproic acid, a branched short-chain fatty acid, has numerous action mechanisms which turn it into a broad spectrum anticonvulsant drug and make its use possible in some other pathologies such as bipolar disorder. It is extensively metabolized in liver, representing β-oxidation in the mitochondria one of its main metabolic route (40%). Carnitine is responsible for its entry into the mitochondria as any other fatty acid. Long-term high-dose VPA therapy or acute VPA overdose induces carnitine depletion, resulting in high levels of ammonia in blood. As a high correlation between salivary valproic acid levels and plasma ultrafiltrate levels was found in humans, saliva becomes a promising monitoring fluid in order to study valproic acid pharmacokinetics and its toxic effect. Extended-release (twice daily) formulations of valproic acid or carnitine supplementation are the proposed two therapeutic strategies in order to reverse hyperammonemia.