Summary
Acute toxicity in the setting of valproic acid (valproate sodium) overdose is in most cases benign and readily reversible. However, serious toxicity has been reported. We present a case of accidental acute valproic acid overdose in a 26-month-old female, in whom serious neurological, metabolic, haematological and respiratory sequelae occurred. The major toxicity observed was delayed cerebral oedema. We also present data not previously reported, which describes the pharmacokinetic disposition of valproic acid and several of its metabolites during the course of this acute overdose. A comparison of an enzyme immunoassay and gas liquid chromatographic methodologies for measuring valproic acid in this setting is also presented. It appears that the 2-EN-valproic acid metabolite plays a role in the neurological toxicity.
Similar content being viewed by others
References
Barre J, Chamourad JM. Equilibrium dialysis, ultrafiltration, and ultracentrifugation compared for determining the plasma protein binding characteristics of valproic acid. Clinical Chemistry 31: 60–64, 1985.
Bigler D. Neurological sequelae after intoxication with sodium valproate. Acta Neurologica Scandinavica 72: 351–352, 1985.
Boillot A, Bourgeouis F, Barale F, Lenys R, Daoudal P, et al. Atteinte médullaire mortelle au cours d’une intoxication aiguë voluntaire par dipropylacetate de sodium. Nouvelle Presse Medicale 10: 2038, 1981.
Connacher AA, Macnab JP, Moody JP, Jung RT. Fatality due to massive overdose of sodium valproate. Scottish Medical Journal 32: 85–86, 1987.
Eadie MJ, Hooper WD, Dickinson RG. Valproate associated hepatotoxicity and its biochemical mechanisms. Medical Toxicology 3: 85–106, 1988.
Eeg-Olofsson O, Linskog U. Acute intoxication with valproate. Lancet 2: 1306, 1982.
Faller JP, Girardel M, Sauder P, Haegy JM, Simon G. Intoxication aiguë par le valproate de sodium. Nouvelle Presse Medicale 10: 3323, 1981.
Garnier R, Fournier E. Intoxication associated with sodium valproate. Nouvelle Presse Medicale 11: 678, 1982.
Gourru JL. Intoxication aiguë massive par le valproate de sodium: à propos d’une observation d’intoxication voluntaire mortelle. Medical Thesis, University of Lyon 1, 1981.
Hinzte G, Klein HH, et al. A case of valproate intoxication with excessive brain edema. Klinische Wochenschrift 65: 424–427, 1987.
Howell SP, Hazelton GA, et al. Depletion of hepatic UDP-glucuronic acid by drugs that are glucuronidated. Journal of Pharmacology and Experimental Therapeutics 236: 610–614, 1986.
Karlssen RL, Kett K, Henriksen O. Intoxication with sodium valproate: a case report. Acta Medica Scandinavica 213: 405–406, 1983.
Lakhani M, McMurdo M. Survival after severe self poisoning with sodium valproate. Postgraduate Medical Journal 62: 409–410, 1986.
Loscher W, Nau H. Valproic acid: metabolite concentrations in plasma and brain, anticonvulsant activity and effects on GABA metabolism during subacute treatment in mice. Archives Internationales de Pharmacodynamie et de Thérapie 257: 20–31, 1982.
Loscher W, Nau H. Distribution of valproic acid and its metabolites in various brain areas of dogs and rats after acute and prolonged treatment. Journal of Pharmacology and Experimental Therapeutics 226: 845–854, 1983.
Loscher W, Nau H. Pharmacological evaluation of various metabolites and analogues of valproic acid. Neuropharmacology 24: 427–435, 1985.
Loscher W, Nau H, et al. Penetration of valproate and its active metabolites into cerebrospinal fluid of children with epilepsy. Epilepsia 29: 311–316, 1988.
Mortensen PB, Hausen HE, Pedersen B, Hartmann-Anderson F, Husted SE. Acute valproate intoxication: biochemical investigations and hemodialysis treatment. International Journal of Clinical Pharmacology Therapy and Toxicology 21: 64–68, 1983.
Pollack GM, McHugh WB, et al. Accumulation and washout kinetics of valproic acid and its active metabolites. Journal of Clinical Pharmacology 26: 668–676, 1986.
Rimmer EM, Richens A. An update on sodium valproate. Pharmacotherapy 5: 171–184, 1985.
Schnabel R, Rambeck B, Janssen F. Fatal intoxication with sodium valproate. Lancet 1: 221–222, 1984.
Steiman GS, Woerpel RW, Sherard ES. Treatment of accidental sodium valproate overdose with an opiate antagonist. Annals of Neurology 6: 274, 1979.
Van Der Merwe AC, Albrecht CF, Brink MS, Caetzee AR. Sodium valproate poisoning: a case report. South African Medical Journal 67: 735–736, 1985.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dupuis, R.E., Lichtman, S.N. & Pollack, G.M. Acute Valproic Acid Overdose. Drug-Safety 5, 65–71 (1990). https://doi.org/10.2165/00002018-199005010-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-199005010-00006