title: Acute valproate poisoning: pharmacokinetics, alteration in fatty acid metabolism, and changes during therapy.
abstract: The clinical features, complications, and pharmacokinetics of intentional acute valproic acid (VPA) overdoses are described. Alteration in fatty acid metabolism is evaluated and therapy-induced changes are discussed. Central nervous system features were the predominant clinical manifestations (6/6), followed by respiratory failure (5/6) and multiorgan failure (2/6). Mechanical ventilation was required in 5 of 6 patients because of respiratory depression or deep coma. Hemodialysis was applied in 4/6 of the cases due to hyperammonemia, worsening neurologic condition, or organ dysfunction. Cerebral edema and hemorrhagic pancreatitis ensued in 2/6 of the patients and ICU mortality was 2/6. VPA peak levels ranged from 520 to 1700 mg/L with a mean of 1127 mg/L. Ammonia was elevated in all cases with a mean of 550 microg/dL. All patients showed signs of impaired mitochondrial beta-oxidation with increase of medium- and long-chain acylcarnitines in serum. Severe VPA overdose is associated with a high mortality rate requiring early medical interventions. Beside supportive intensive care, hemodialysis can be considered as an adjunctive measure.
authors: Department of Toxicology, Klinikum rechts der Isar, Technical University Munich, Germany. Florian.Eyer@t-online.de
authors: Florian
authors: F
authors: Eyer
authors: Norbert
authors: N
authors: Felgenhauer
authors: Klaus
authors: K
authors: Gempel
authors: Werner
authors: W
authors: Steimer
authors: Klaus-Dieter
authors: KD
authors: Gerbitz
authors: Thomas
authors: T
authors: Zilker
mesh_terms: D000927:Anticonvulsants / Q000493:pharmacokinetics* / Q000506:poisoning*; D001929:Brain Edema / Q000139:chemically induced; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D062787:Drug Overdose / Q000378:metabolism / Q000628:therapy; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced; D008297:Male; D008928:Mitochondria / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010195:Pancreatitis / Q000139:chemically induced; D006435:Renal Dialysis; D014635:Valproic Acid / Q000493:pharmacokinetics* / Q000506:poisoning*
chemical_list: D000927:Anticonvulsants; D005227:Fatty Acids; C116917:acylcarnitine; D014635:Valproic Acid; D002331:Carnitine