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It is extensively metabolized in liver, representing<jats:italic>\u03b2<\/jats:italic>-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.<\/jats:p>","DOI":"10.1155\/2014\/217269","type":"journal-article","created":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T17:04:00Z","timestamp":1398791040000},"page":"1-7","source":"Crossref","is-referenced-by-count":54,"title":["Hyperammonemia Associated with Valproic Acid Concentrations"],"prefix":"10.1155","volume":"2014","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8459-4859","authenticated-orcid":true,"given":"Marta","family":"V\u00e1zquez","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Department, Faculty of Chemistry, Universidad de la Rep\u00fablica, Avenida General Flores 2124, P.O. 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