title: Hyperammonemia associated with valproic acid concentrations.
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.
authors.affiliation: Pharmaceutical 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.
authors.forename: Marta
authors.identifier: 0000-0002-8459-4859
authors.initials: M
authors.lastname: Vázquez
authors.affiliation: Pharmaceutical 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.
authors.forename: Pietro
authors.identifier: 0000-0001-6756-1601
authors.initials: P
authors.lastname: Fagiolino
authors.affiliation: Pharmaceutical 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.
authors.forename: Cecilia
authors.identifier: 0000-0002-9452-2111
authors.initials: C
authors.lastname: Maldonado
authors.affiliation: Pharmaceutical 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.
authors.forename: Ismael
authors.identifier: 0000-0002-3074-7637
authors.initials: I
authors.lastname: Olmos
authors.affiliation: Pharmaceutical 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.
authors.forename: Manuel
authors.identifier: 0000-0002-0484-6367
authors.initials: M
authors.lastname: Ibarra
authors.affiliation: Pharmaceutical 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.
authors.forename: Silvana
authors.initials: S
authors.lastname: Alvariza
authors.affiliation: Pharmaceutical 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.
authors.forename: Natalia
authors.identifier: 0000-0002-5541-6316
authors.initials: N
authors.lastname: Guevara
authors.affiliation: Pharmaceutical 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.
authors.forename: Laura
authors.initials: L
authors.lastname: Magallanes
authors.affiliation: "Sanatorio Canzani" Hospital, Banco de Previsión Social, Martín García 1363, 11800 Montevideo, Uruguay.
authors.forename: Ivette
authors.identifier: 0000-0003-0906-7626
authors.initials: I
authors.lastname: Olano
mesh_terms: D000293:Adolescent; D000328:Adult; D000641:Ammonia / Q000097:blood; D001714:Bipolar Disorder / Q000188:drug therapy; D002331:Carnitine / Q000008:administration & dosage / Q000737:chemistry; D002648:Child; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000187:drug effects; D012463:Saliva / Q000187:drug effects; D014635:Valproic Acid / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D055815:Young Adult
chemical_list: D014635:Valproic Acid; D000641:Ammonia; D002331:Carnitine