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Published on: November 8, 2018
Hyperammonemia associated with valproic acid concentrations
Marta Vázquez1, Pietro Fagiolino1, Cecilia Maldonado1
1Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la República, Avenida General Flores 2124, P.O. Box 1157, 11800 Montevideo, Uruguay ; Therapeutic Drug Monitoring Service, "Dr. Manuel Quintela" Clinical Hospital, Universidad de la República, Avenida Italia s/n, 11609 Montevideo, Uruguay.
Abstract:
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.
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