2,701
Views
181
CrossRef citations to date
0
Altmetric
Research Article

Valproic Acid Toxicity: Overview and Management

Pages 789-801 | Published online: 26 Nov 2002

REFERENCES

  • Pinkston R., Walker L.A. Multiorgan System Failure Caused by Valproic Acid Toxicity. Am. J. Emerg. Med. 1997; 15: 504–506
  • Davis L.L., Ryan W., Adinoff B., Petty F. Comprehensive Review of the Psychiatric Uses of Valproate. J. Clin. Psychopharmacol. 2000; 20(Suppl. 1)1S–7S
  • Evans D.L. Bipolar Disorder: Diagnostic Challenges and Treatment Considerations. J. Clin. Psychiatry 2000; 61(Suppl. 13)26–31
  • Goldberg J.F. Treatment Guidelines: Current and Future Management of Bipolar Disorder. J. Clin. Psychiatry 2000; 61(Suppl. 13)12–18
  • Nemeroff C.B. An Ever-Increasing Pharmacopoeia for the Management of Patients with Bipolar Disorder. J. Clin. Psychiatry 2000; 61(Suppl. 13)19–25
  • Mathew N.T., Kailasam J., Meadors L., Chernyschev O., Gentry P. Intravenous Valproate Sodium (Depacon) Aborts Migraine Rapidly: A Preliminary Report. Headache 2000; 40: 720–723
  • Norton J. Use of Intravenous Valproate Sodium in Status Migraine. Headache 2000; 40: 755–757
  • Kinze S., Clauss M., Reuter U., Wolf T., Dreier J.P., Einhaupl K.M., Arnold G. Valproic Acid Is Effective in Migraine Prophylaxis at Low Serum Levels: A Prospective Open-Label Study. Headache 2001; 41: 774–778
  • Hardy J.R., Rees E.A.J., Gwilliam B., Ling J., Broadley K., A'Hern R. A Phase II Study to Establish the Efficacy and Toxicity of Sodium Valproate in Patients with Cancer-Related Neuropathic Pain. J. Pain Symptom Manag. 2001; 21: 204–209
  • Litovitz T.L., Klein-Schwartz W., White S., Cobaugh D.J., Youniss J., Omslaer J.C., Drab A., Benson B.E. 2000 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am. J. Emerg. Med. 2001; 19: 337–395
  • Litovitz T.L., Felberg L., White S., Klein-Schwartz W. 1995 Annual Report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am. J. Emerg. Med. 1996; 14: 487–537
  • Litovitz T.L., Bailey K.M., Schmitz B.F., Holm K.C., Klein-Schwartz W. 1990 Annual Report of the American Association of Poison Control Centers National Data Collection System. Am. J. Emerg. Med. 1991; 9: 461–509
  • Klotz U., Antonin K.H. Pharmacokinetics and Bioavailability of Sodium Valproate. Clin. Pharmacol. Ther. 1977; 21: 736–743
  • Kandrotas R.J., Love J.M., Gal P., Oles K.S. The Effect of Hemodialysis and Hemoperfusion on Serum Valproic Acid Concentration. Neurology 1990; 40: 1456–1458
  • Nau H., Loscher W. Valproic Acid and Metabolites: Pharmacological and Toxicological Studies. Epilepsia 1984; 25(S1)S14–S22
  • Kane S.L., Constantiner M., Staubus A.E., Meinecke C.D., Sedor J.R. High-Flux Hemodialysis Without Hemoperfusion Is Effective in Acute Valproic Acid Overdose. Ann. Pharmacother. 2000; 34: 1146–1151
  • Farrar H.C., Herold D.A., Reed M.D. Acute Valproic Acid Intoxication: Enhanced Drug Clearance with Oral-Activated Charcoal. Crit. Care Med. 1993; 21: 299–301
  • Al-Shareef A., Buss D.C., Shetty H.G.M., Ali N., Routledge P.A. The Effect of Repeated-Dose Activated Charcoal on the Pharmacokinetics of Sodium Valproate in Healthy Volunteers. Br. J. Clin. Pharmacol. 1997; 43: 109–111
  • Graudins A., Aaron C.K. Delayed Peak Serum Valproic Acid in Massive Divalproex Overdose—Treatment with Charcoal Hemoperfusion. J. Toxicol. Clin. Toxicol. 1996; 34: 335–341
  • Duarte J., Macias S., Coria F., Fernandez E., Claveria L.E. Valproate-Induced Coma: Case Report and Literature Review. Ann. Pharmacother. 1993; 27: 582–583
  • Tatsuhara T., Muro H., Matsuda Y., Imai Y. Determination of Valproic Acid and it Metabolites by Gas Chromatography–Mass Spectrometry with Selected Ion Monitoring. J. Chromatogr. 1987; 399: 183–195
  • Hamer H.M., Knake S., Schomburg M.A., Rosenow F. Valproate-Induced Hyperammonemic Encephalopathy in the Presence of Topiramate. Neurology 2000; 54: 230–232
  • Spiller H.A., Krenzelok E.P., Klein-Schwartz W., Winter M.L., Weber J.A., Sollee D.R., Bangh S.A., Griffith J.R. Multicenter Case Series of Valproic Acid Ingestion. J. Toxicol. Clin. Toxicol. 1999; 37: 637
  • Ingels M., Johnson C., Rangan C., Cantrell L., Beauchamp J., Clark R.F. Retrospective Study of Delayed Valproic Acid Toxicity. Acad. Emerg. Med. 2000; 7: 499
  • Franssen E.J., van Essen G.G., Portman A.T., de Jong J., Go G., Stegeman C.A., Uges D.R. Valproic Acid Toxicokinetics: Serial Hemodialysis and Hemoperfusion. Ther. Drug Monit. 1999; 21: 289–292
  • Dupuis R.E., Lichtman S.N., Pollack G.M. Acute Valproic Acid Overdose. Clinical Course and Pharmacokinetic Disposition of Valproic Acid and Metabolites. Drug Saf. 1990; 5: 65–71
  • Chadwick D.W. Concentration–Effect Relationships of Valproic Acid. Clin. Pharmacokinet. 1985; 10: 155–163
  • Andersen G., Ritland S. Life Threatening Intoxication with Sodium Valproate. J. Toxicol. Clin. Toxicol. 1995; 33: 279–284
  • Johnson L.Z., Martinez I., Fernandez M.C., Davis C.P., Kasinath B.S. Successful Treatment of Valproic Acid Overdose with Hemodialysis. Am. J. Kidney Dis. 1999; 33: 786–789
  • Mortensen P.B., Hansen H.E., Pedersen B., Hartmann-Andersen F., Husted S.E. Acute Valproate Intoxication: Biochemical Investigations and Hemodialysis Treatment. Int. J. Clin. Pharmacol. Ther. Toxicol. 1983; 21: 64–68
  • Nau H., Wittfoht W. Valproic Acid and Several Metabolites: Quantitative Determination in Serum, Urine, Breast Milk, and Tissues by Gas Chromatography–Mass Spectrometry Using Selected Ion Monitoring. J. Chomatogr. 1981; 226: 69–78
  • Jakobs C., Loscher W. Identification of Metabolites of Valproic Acid in Serum of Humans, Dog, Rat, and Mouse. Epilepsia 1978; 19: 591–602
  • Cotariu D., Zaidman J.L. Valproic Acid and the Liver. Clin. Chem. 1988; 34(5)890–897
  • Raskind J.Y., El-Chaar G.M. The Role of Carnitine Supplementation During Valproic Acid Therapy. Ann. Pharmacother. 2000; 34: 630–638
  • Ishikura H., Matsuo N., Matsubara M., Ishihara T., Takeyama N., Tanaka T. Valproic Acid Overdose and l-Carnitine Therapy. J. Anal. Toxicol. 1996; 20: 55–58
  • Johannessen C.U. Mechanisms of Action of Valproate: A Commentatory. Neurochem. Int. 2000; 37: 103–110
  • McLean M.J., MacDonald R.L. Sodium Valproate, But Not Ethosuximide, Produces Use- and Voltage-Dependent Limitation of High Frequency Repetitive Firing of Action Potentials of Mouse Central Neurons in Cell Culture. J. Pharmacol. Exp. Ther. 1986; 237: 1001–1011
  • Farrant M., Webster R.A. Neuronal Activity, Amino Acid Concentration, and Amino Acid Release in the Substantia Nigra of the Rat After Sodium Valproate. Brain Res. 1986; 386: 1–11
  • Albus H., Williamson R. Electrophysical Analysis of the Action of Valproate on Pyramidal Neurons in the Rat Hippocampal Slice. Epilepsia 1998; 39: 124–139
  • Hariton C., Ciesielski L., Simler S., Valli M., Jadot G., Gobaille S., Mesdjian E., Mandel P. Distribution of Sodium Valproate and GABA Metabolism in CNS of the Rat. Biopharm. Drug Dispos. 1984; 5: 409–414
  • Keane P.E., Simiand J., Morre M. Comparison of the Pharmacological and Biochemical Profiles of Valproic Acid (VPA) and Its Cerebral Metabolite (2-en-VPA) After Oral Administration in Mice. Methods Find. Exp. Clin. Pharmacol. 1985; 7: 83–86
  • Keane P.E., Morre M. Effect of Valproate on Brain GABA: Comparison with Various Medium Chain Fatty Acids. Pharmacol. Res. Commun. 1985; 17: 547–555
  • Swann A.C. Major Systemic Toxicities and Side Effects of Anticonvulsants. J. Clin. Psychiatry 2001; 62(Suppl. 14)16–21
  • Khoo S.H., Leyland M.J. Cerebral Edema Following Acute Sodium Valproate Overdose. J. Toxicol. Clin. Toxicol. 1992; 30: 209–214
  • Matsumoto J., Ogawa H., Maeyama R., Okudaira K., Shinka T., Kuhara T., Matsumoto I. Successful Treatment by Direct Hemoperfusion of Coma Possibly Resulting from Mitochondrial Dysfunction in Acute Valproate Intoxication. Epilepsia 1997; 38: 950–953
  • Triggs W.J., Gilmore R.L., Millington D.S., Cibula J., Bunch T.S., Harman E. Valproate-Associated Carnitine Deficiency and Malignant Cerebral Edema in the Absence of Hepatic Failure. Int. J. Clin. Pharmacol. Ther. 1997; 35: 353–356
  • Janssen F., Rambeck B., Schnabel R. Acute Valproate Intoxication with Fatal Outcome in an Infant. Neuropediatrics 1985; 16: 235–238
  • Berthelot-Moritz F., Chadda K., Chanavaz I., Leroy J.P., Droy J.M., Bonmarchand G., Leroy J. Fatal Sodium Valproate Poisoning. Intensive Care Med. 1997; 23: 599
  • Loscher W., Nau H. Pharmacological Evaluation of Various Metabolites and Analogues of Valproic Acid. Anticonvulsant and Toxic Potencies in Mice. Neuropharmacology 1985; 24: 427–435
  • Murakami K., Sugimoto T., Woo M., Nishida N., Muro H. Effect of l-Carnitine Supplementation on Acute Valproate Intoxication. Epilepsia 1996; 37: 687–689
  • Blei A.T. Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited. Metab. Brain Dis. 2001; 16: 85–94
  • Albrecht J., Dolinska M. Glutamine as a Pathogenic Factor in Hepatic Encephalopathy. J. Neurosci. Res. 2001; 65: 1–5
  • Hertz L., Yu A.C.H., Kala G., Schousboe A. Neuronal-Astrocytic and Cytosolic-Mitochondrial Metabolite Trafficking During Brain Activation, Hyperammonemia, and Energy Deprivation. Neurochem. Int. 2000; 37: 83–102
  • Marcaida G., Felipo V., Hermenegildo C., Minana M.D., Grisolia S. Acute Ammonia Toxicity Is Mediated by the NMDA Type of Glutamate Receptors. FEBS Lett. 1992; 13(296)67–68
  • Connacher A.A., MacNab M.S., Moody J.P., Jung R.T. Fatality Due to Massive Overdose of Sodium Valproate. Scott. Med. J. 1987; 32: 85–86
  • Camfield P.R., Bagnell P., Camfield C.S., Tibbles J.A. Pancreatitis Due to Valproic Acid. Lancet 1979; 1: 1198–1199
  • Batalden P.B., Van Dyne B.J., Cloyd J. Pancreatitis Associated with Valproic Acid Therapy. Pediatrics 1979; 64: 520–522
  • Binek J., Hany A., Heer M. Valproic-Acid-Induced Pancreatitis: Case Report and Review of the Literature. J. Clin. Gastroenterol. 1991; 3: 690–693
  • Rosenberg H.K., Ortega W. Hemorrhagic Pancreatitis in a Young Child Following Valproic Acid Therapy. Clin. Pediatr. 1987; 26: 98–101
  • Caparros-Lefebvre D., Lecomte-Houcke M., Pruvot F.R., Declerck N., Paris J.C., Petit H. Unusual Electronmicroscopic Changes in Valproate-Associated Liver Failure. Lancet 1993; 341: 1604
  • Gerber N., Dickinson R.G., Harland R.C., Lynn R.K., Houghton L.D., Antonias J.I., Schimschock J.C. Reye-like Syndrome Associated with Valproic Acid Therapy. J. Pediatr. 1979; 95: 142–144
  • Suchy F.J., Balistreri W.F., Buchino J.J., Sondheimer J.M., Bates S.R., Kearns G.L., Stull J.D., Bove K.E. Acute Hepatic Failure Associated with the Use of Sodium Valproate. N. Engl. J. Med. 1979; 300: 962–966
  • Appleton R.E., Farrell K., Applegarth D.A., Dimmick J.E., Wong L.T., Davidson A.G. The High Incidence of Valproate Hepatotoxicity in Infants May Relate to Familial Metabolic Defects. Can. J. Neurol. Sci. 1990; 17: 145–148
  • Krahenbuhl S., Brandner S., Kleinle S., Liechti S., Straumann D. Mitochondrial Diseases Represent a Risk Factor for Valproate-Induced Fulminant Liver Failure. Liver 2000; 20: 346–348
  • Chabrol B., Mancini J., Chretien D., Rustin P., Munnich A., Pinsard N. Valproate-Induced Hepatic Failure in a Case of Cytochrome C Oxidase Deficiency. Eur. J. Pediatr. 1994; 153: 133–135
  • Kochen W., Schneider A., Ritz A. Abnormal Metabolism of Valproic Acid in Fatal Hepatic Failure. Eur. J. Pediatr. 1983; 141: 30–35
  • Kuhara T., Inoue Y., Matsumoto M., Shinka T., Matsumoto I., Kawahara N., Sakura N. Markedly Increased ω-Oxidation of Valproate in Fulminant Hepatic Failure. Epilepsia 1990; 31: 214–217
  • Kesterson J.W., Granneman G.R., Machinist J.M. The Hepatotoxicity of Valproic Acid and Its Metabolites in Rats. I. Toxicologic, Biochemical and Histopathologic Studies. Hepatology 1984; 4: 1143–1152
  • Rettie A.E., Rettenmeier A.W., Howald W.N., Baillie T.A. Cytochrome P-450-Catalyzed Formation of Delta 4-VPA, a Toxic Metabolite of Valproic Acid. Science 1987; 235: 890–893
  • Kulick S.K., Kramer D.A. Hyperammonemia Secondary to Valproic Acid as a Cause of Lethargy in a Postictal Patient. Ann. Emerg. Med. 1993; 22: 610–612
  • Thabet H., Brahmi N., Amamou M., Ben Salah N., Hedhili N. Hyperlactatemia and Hyperammonemia as Secondary Effects of Valproic Acid Poisoning. Am. J. Emerg. Med. 2000; 18: 508
  • Lee W.L., Yang C.C., Deng J.F., Chen Y.F., Lin H.D., Wang P.H. A Case of Severe Hyperammonemia and Unconsciousness Following Sodium Valproate Intoxication. Vet. Hum. Toxicol. 1998; 40: 346–348
  • Hjelm M., Oberholzer V., Seakins J., Thomas S., Kay J.D.S. Valproate-Induced Inhibition of Urea Synthesis and Hyperammonaemia in Healthy Subjects. Lancet 1986; 2: 859
  • Rawat S., Borkowski W.J., Swick H.M. Valproic Acid and Secondary Hyperammonemia. Neurology 1981; 31: 1173–1174
  • Coulter D.L. Carnitine Deficiency in Epilepsy: Risk Factors and Treatment. J. Child Neurol. 1995; 10(Suppl. 2)S32–S39
  • Rumbach L., Cremel G., Marescaux C., Warter J.M., Waksman A. Valproate-Induced Hyperammonemia of Renal Origin. Effect of Valproate on Glutamine Transport in Rat Kidney Mitochondria. Biochem. Pharmacol. 1989; 38: 3963–3967
  • Coulter D.L., Allen R.J. Secondary Hyperammonemia: A Possible Mechanism for Valproate Encephalopathy. Lancet 1980; 1310–1311
  • Coude F.X., Rabier D., Cathelineau L., Grimber G., Parvy P., Kamoun P.P. A Mechanism for Valproate-Induced Hyperammonemia. Pediatr. Res. 1981; 15: 974–975
  • Paganini M., Zaccara G., Moroni F. Lack of Relationship Between Sodium Valproate-Induced Adverse Effects and the Plasma Concentration of Its Metabolite 2-Propylpenten-4-oic Acid. Eur. J. Clin. Pharmacol. 1987; 32: 219–222
  • Kondo T., Ishida M., Kaneko S., Hirano T., Otani K., Fukushima Y., Muranaka H., Koide N., Yokoyama M., Nakata S., Kudo H. Is 2-Propyl-4-pentenoic acid, a Hepatotoxic Metabolite of Valproate, Responsible for Valproate-Induced Hyperammonemia?. Epilepsia 1992; 33: 550–554
  • Dreifuss F.E., Santilli N., Langer D.H., Sweeney K.P., Moline K.A., Menander K.B. Valproic Acid Hepatic Fatalities: A Retrospective Review. Neurology 1987; 37: 379–385
  • Murakami K., Sugimoto T., Nishida N., Kobayashi Y., Kuhura T., Matsumoto I. Abnormal Metabolism of Carnitine and Valproate in a Case of Acute Encephalopathy During Chronic Valproate Therapy. Brain Dev. 1992; 14: 178–181
  • Beversdorf D., Allen C., Nordgren R. Valproate-Induced Encephalopathy Treated with Carnitine in an Adult. J. Neurol. Neurosurg. Psychiatry 1996; 61: 211
  • De Vivo D.C., Bohan T.P., Coulter D.L., Dreifuss F.E., Greenwood R.S., Nordli D.R., Shields W.D., Stafstrom C.E., Tein I. l-Carnitine Supplementation in Childhood Epilepsy: Current Perspectives. Epilepsia 1998; 39: 1216–1225
  • Coulter D.L. Carnitine, Valproate and Toxicity. J. Child Neurol. 1991; 6: 7–14
  • Thom H., Carter P.E., Cole G.F., Stevenson K.L. Ammonia and Carnitine Concentrations in Children Treated with Sodium Valproate Compared with Other Anticonvulsant Drugs. Dev. Med. Child Neurol. 1991; 33: 795–802
  • Takeuchi T., Sugimoto T., Nishida N., Kobayashi Y. Protective Effect of d,l-Carnitine on Valproate-Induced Hyperammonemia and Hypoketonemia in Primary Cultured Rat Hepatocytes. Biochem. Pharmacol. 1988; 37: 2255–2258
  • Ponchaut S., van Hoof F., Veitch K. In Vitro Effects of Valproate and Valproate Metabolites on Mitochondrial Oxidations. Relevance of CoA Sequestration to the Observed Inhibitions. Biochem. Pharmacol. 1992; 43: 2435–2442
  • Baldwin G.S., Abbott F.S., Nau H. Binding of a Valproate Metabolite to the Trifunctional Protein of Fatty Acid Oxidation. FEBS Lett. 1996; 384: 58–60
  • Alonso E., Girbes J., Garcia-Espana A., Rubio V. Changes in Urea Cycle-Related Metabolites in the Mouse After Combined Administration of Valproic Acid and an Amino Acid Load. Arch. Biochem. Biophys. 1989; 272: 267–273
  • Thurston J.H., Carroll J.E., Hauhart R.E., Schiro J.A. A Single Therapeutic Dose of Valproate Affects Liver Carbohydrate, Fat, Adenylate, Amino Acid, Coenzyme A, and Carnitine Metabolism in Infant Mice: Possible Clinical Significance. Life Sci. 1985; 36: 1643–1651
  • Beauchamp J., Olson K. Valproic Acid Overdoses: A Retrospective Study Comparing Serum Drug Levels and the Incidence of Adverse Outcomes. J. Toxicol. Clin. Toxicol. 1999; 37: 637–638
  • Roodhooft A.M., Van Dam K., Haentjens D., Verpooten G.A., Van Acker K.J. Acute Sodium Valproate Intoxication: Occurrence of Renal Failure and Treatment with Haemoperfusion–Haemodialysis. Eur. J. Pediatr. 1990; 149: 363–364
  • Settle E.J., Jr. Valproic Acid-Associated Encephalopathy with Coma. Am. J. Psychiatr. 1995; 152: 1236–1237
  • Barrueto F., Jr., Hack J.B. Hyperammonemia and Coma Without Hepatic Dysfunction Induced by Valproate Therapy. Acad. Emerg. Med. 2001; 8: 999–1001
  • Chyka P.A., Seger D. Position Statement: Single-Dose Activated Charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J. Toxicol. Clin. Toxicol. 1997; 35: 721–741
  • Anon. Position Statement and Practice Guidelines on the Use of Multi-dose Activated Charcoal in the Treatment of Acute Poisoning. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists. J. Toxicol. Clin. Toxicol. 1999; 37: 731–751
  • Von Bardeleben R.S., Sturer A., Weilemann L.S. Valproic Acid Intoxications in 96 Documented Cases 1995–1998: The Role of Hemoperfusion in Therapy. J. Toxicol. Clin. Toxicol. 1998; 36: 471–472
  • Matsumoto J., Ogawa H., Maeyama R., Okudaira K., Shinka T., Kuhara T., Matsumoto I. Successful Treatment by Direct Hemoperfusion of Coma Possibly Resulting from Mitochondrial Dysfunction in Acute Valproate Intoxication. Epilepsia 1997; 38: 950–953
  • Tank J.E., Palmer B.F. Simultaneous “In Series” Hemodialysis and Hemoperfusion in the Management of Valproic Acid Overdose. Am. J. Kidney Dis. 1993; 22: 341–344
  • Ruskoky D., Holmes C., Schauben J. Utilization of Hemodialysis to Enhance Valproic Acid (VPA) Elimination. J. Toxicol. Clin. Toxicol. 1999; 37: 636
  • Graeme K., Higgins T., Curry S., Kunkel D. Markedly Elevated Valproate Levels Do Not Serve as an Indication for Hemodialysis or Hemoperfusion. J. Toxicol. Clin. Toxicol. 1999; 37: 636
  • Steiman G.S., Woerpel R.W., Sherard E.S., Jr. Treatment of Accidental Sodium Valproate Overdose with an Opiate Antagonist. Ann. Neurol. 1979; 6: 274
  • Alberto G., Erickson T., Popiel R., Narayanan M., Hryhorczuk D. Central Nervous System Manifestations of a Valproic Acid Overdose Responsive to Naloxone. Ann. Emerg. Med. 1989; 18: 889–891
  • Montero F.J. Naloxone in the Reversal of Coma Induced by Sodium Valproate. Ann. Emerg. Med. 1999; 33: 357–358
  • Espinoza O., Maradei I., Ramirez M., Pascuzzo-Lima C. An Unusual Presentation of Opioid-like Syndrome in Pediatric Valproic Acid Poisoning. Vet. Hum. Toxicol. 2001; 43: 178–179
  • Takeuchi T., Sugimoto T., Nishida N., Kobayashi Y. Protective Effect of d,l-Carnitine on Valproate-Induced Hyperammonemia and Hypoketonemia in Primary Cultured Rat Hepatocytes. Biochem. Pharmacol. 1988; 37: 2255–2258
  • Anon. Carnitor. Physician's Desk Reference. 54th Ed., Medical Economic Company, Montvale, NJ 2000
  • Sztajnkrycer M.D., Seaglione J.M., Bond G.R. Valproate-Induced Hyperammonemia: Preliminary Evaluation of Ammonia Elimination with Carnitine Administration. J. Toxicol. Clin. Toxicol. 2001; 39: 497
  • Thole D., Bagnasco T., Lovecchio F. Delayed Absorption of Valproic Acid Resulting in Coma. J. Toxicol. Clin. Toxicol. 2001; 39: 497

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.