Hyperammonemia Associated with Valproic Acid Concentrations

Abstract EN

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.