Fomepizole

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Abstract

Fomepizole is the generic drug name for the chemical 4-methylpyrazole (4-MP) now widely available in Europe and North America for the treatment of methanol and ethylene glycol poisoning. It is a potent inhibitor of alcohol dehydrogenase (ADH), with an affinity more than 1000 times that of the toxic alcohols [1]. Fomepizole has demonstrated efficacy in vivo against the conversion of methanol and ethylene glycol to their toxic metabolites in animal models [2, 3], where it reversed an already-developed metabolite accumulation and severe metabolic acidosis without dialysis. Because of its high safety profile and ease of use in human patients, fomepizole has rapidly replaced ethanol for ADH-inhibitory therapy in methanol and ethylene glycol poisoning [4]. Fomepizole may also have clinical utility in treating similar intoxications, such as those of glycol ethers, diethylene glycol, and propylene glycol [5–7], as well as in ethanol-disulfiram interactions [8].

Keywords

Diethylene Glycol Glycol Ether Severe Metabolic Acidosis Methanol Poisoning Toxic Alcohol 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. 1.
    Li TK, Theorell H. Human liver alcohol dehydrogenase: inhibition by pyrazole and pyrazole analogs. Acta Chem Scand A. 1969;23:892–902.CrossRefGoogle Scholar
  2. 2.
    McMartin KE, Makar AB, Martin G, Palese M, Tephly TR. Methanol poisoning. I. The role of formic acid in the development of metabolic acidosis in the monkey and the reversal by 4-methylpyrazole. Biochem Med. 1975;13:319–33.CrossRefPubMedGoogle Scholar
  3. 3.
    Clay KL, Murphy RC. On the metabolic acidosis of ethylene glycol intoxication. Toxicol Appl Pharmacol. 1977;39:39–49.CrossRefPubMedGoogle Scholar
  4. 4.
    Barceloux DG, Krenzelok EP, Olson K, Watson W. American academy of clinical toxicology practice guidelines on the treatment of ethylene Glycol poisoning. Ad Hoc committee. J Toxicol Clin Toxicol. 1999;37:537–60.CrossRefPubMedGoogle Scholar
  5. 5.
    Ghanayem BI, Burka LT, Matthews HB. Metabolic basis of ethylene glycol monobutyl ether (2-butoxyethanol) toxicity: role of alcohol and aldehyde dehydrogenases. J Pharmacol Exp Ther. 1987;242:222–31.PubMedGoogle Scholar
  6. 6.
    Van de Wiele B, Rubinstein E, Peacock W, Martin N. Propylene glycol toxicity caused by prolonged infusion of etomidate. J Neurosurg Anesthesiol. 1995;7:259–62.CrossRefPubMedGoogle Scholar
  7. 7.
    Besenhofer LM, McLaren MC, Latimer B, Bartels M, Filary MJ, Perala AW, McMartin KE. Role of tissue metabolite accumulation in the renal toxicity of diethylene glycol. Toxicol Sci. 2011;123:374–83.CrossRefPubMedGoogle Scholar
  8. 8.
    Lindros KO, Stowell A, Pikkarainen P, Salaspuro M. The disulfiram (Antabuse)-Alcohol reaction in male alcoholics: its efficient management by 4-methylpyrazole. Alcohol Clin Exp Res. 1981;5:528–30.CrossRefPubMedGoogle Scholar
  9. 9.
    Salaspuro MP, Pikkarainen P, Lindros K. Ethanol-induced hypoglycaemia in man: its suppression by the alcohol dehydrogenase inhibitor 4-methylpyrazole. Eur J Clin Invest. 1977;7:487–90.CrossRefPubMedGoogle Scholar
  10. 10.
    Blomstrand R, Kager L. The combustion of triolein-1-14C and its inhibiton by alcohol in man. Life Sci. 1973;13:113–23.CrossRefPubMedGoogle Scholar
  11. 11.
    McMartin KE, Martin-Amat G, Makar AB, Tephly TR. Methanol poisoning: role of formate metabolism in the monkey. In: Thurman RG, Williamson JR, Drott H, Chance B, editors. Alcohol and aldehyde metabolizing systems. New York: Academic; 1977. p. 429–40.CrossRefGoogle Scholar
  12. 12.
    Ingemansson SO. Studies on the effect of 4-methylpyrazole on retinal activity in the methanol poisoned monkey by recording the electroretinogram. Acta Ophthalmol Suppl. 1983;158:1–24.PubMedGoogle Scholar
  13. 13.
    Grauer GF, Thrall MA, Henre BA, Hjelle JJ. Comparison of the effects of ethanol and 4-methylpyrazole on the pharmacokinetics and toxicity of ethylene glycol in the dog. Toxicol Lett. 1987;35:307–14.CrossRefPubMedGoogle Scholar
  14. 14.
    Dial SM, Thrall MA, Hamar DW. 4-Methylpyrazole as treatment for naturally acquired ethylene glycol intoxication in dogs. J Am Vet Med Assoc. 1989;195:73–6.PubMedGoogle Scholar
  15. 15.
    Jacobsen D, Sebastian CS, Blomstrand R, McMartin KE. 4-Methylpyrazole: a controlled study of safety in healthy human subjects after single, ascending doses. Alcohol Clin Exp Res. 1988;12:516–22.CrossRefPubMedGoogle Scholar
  16. 16.
    Jacobsen D, Barron SK, Sebastian CS, Blomstrand R, McMartin KE. Non-linear kinetics of 4-methylpyrazole in healthy human subjects. Eur J Clin Pharmacol. 1989;37:599–604.PubMedGoogle Scholar
  17. 17.
    Jacobsen D, Sebastian CS, Barron SK, Carriere EW, McMartin KE. Effects of 4-methylpyrazole, methanol/ethylene glycol antidote, in healthy humans. J Emerg Med. 1990;8:455–61.CrossRefPubMedGoogle Scholar
  18. 18.
    Jacobsen D, Sebastian CS, Dies DF, Breau RL, Spann EG, Barron SK, McMartin KE. Kinetic interactions between 4-methylpyrazole and ethanol in healthy humans. Alcohol Clin Exp Res. 1996;20:804–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Baud FJ, Bismuth C, Garnier R, Galliot M, Astier A, Maistre G, Soffer M. 4-Methylpyrazole may be an alternative to ethanol therapy for ethylene glycol intoxication in man. J Toxicol Clin Toxicol. 1986;24:463–83.CrossRefPubMedGoogle Scholar
  20. 20.
    Baud FJ, Galliot M, Astier A, Bien DV, Garnier R, Likforman J, Bismuth C. Treatment of ethylene glycol poisoning with intravenous 4-methylpyrazole. N Engl J Med. 1988;319:97–100.CrossRefPubMedGoogle Scholar
  21. 21.
    Burns MJ, Graudins A, Aaron CK, McMartin K, Brent J. Treatment of methanol poisoning with intravenous 4-methylpyrazole. Ann Emerg Med. 1997;30:829–32.CrossRefPubMedGoogle Scholar
  22. 22.
    Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M, Kulig K. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med. 1999;340:832–8.CrossRefPubMedGoogle Scholar
  23. 23.
    Brent J, McMartin K, Phillips S, Aaron C, Kulig K, Methylpyrazole for Toxic Alcohols Study G. Fomepizole for the treatment of methanol poisoning. N Engl J Med. 2001;344:424–9.CrossRefPubMedGoogle Scholar
  24. 24.
    WHO - Essential Medicines List 2013. Available at: http://www.who.int/medicines/publications/essentialmedicines/18th_EML_Final_web_8Jul13.pdf. Accessed on April 5. 2016.
  25. 25.
    Reynier M. Pyrazole inhibition and kinetic studies of ethanol and retinol oxidation catalyzed by rat liver alcohol dehydrogenase. Acta Chem Scand [A]. 1969;23:1119–29.CrossRefGoogle Scholar
  26. 26.
    Makar AB, McMartin KE, Palese M, Tephly TR. Formate assay in body fluids: application in methanol poisoning. Biochem Med. 1975;13:117–26.CrossRefPubMedGoogle Scholar
  27. 27.
    Pietruszko R. Human liver alcohol dehydrogenase--inhibition of methanol activity by pyrazole, 4-methylpyrazole, 4-hydroxymethylpyrazole and 4-carboxypyrazole. Biochem Pharmacol. 1975;24:1603–7.CrossRefPubMedGoogle Scholar
  28. 28.
    McMartin KE, Hedstrom KG, Tolf BR, Ostling-Wintzell H, Blomstrand R. Studies on the metabolic interactions between 4-methylpyrazole and methanol using the monkey as an animal model. Arch Biochem Biophys. 1980;199:606–14.CrossRefPubMedGoogle Scholar
  29. 29.
    Sivilotti ML, Burns MJ, McMartin KE, Brent J. Toxicokinetics of ethylene glycol during fomepizole therapy: implications for management. For the Methylpyrazole for Toxic Alcohols Study Group. Ann Emerg Med. 2000;36:114–25.CrossRefPubMedGoogle Scholar
  30. 30.
    Hovda KE, Andersson KS, Urdal P, Jacobsen D. Methanol and formate kinetics during treatment with fomepizole. Clin Toxicol. 2005;43:221–7.CrossRefGoogle Scholar
  31. 31.
    Hovda KE, Julsrud J, Ovrebo S, Brors O, Jacobsen D. Studies on ethylene glycol poisoning: one patient – 154 admissions. Clin Toxicol (Phila). 2011;49:478–84.CrossRefGoogle Scholar
  32. 32.
    Feierman DE, Cederbaum AI. Inhibition of microsomal oxidation of ethanol by pyrazole and 4-methylpyrazole in vitro. Increased effectiveness after induction by pyrazole and 4-methylpyrazole. Biochem J. 1986;239:671–7.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Feierman DE, Cederbaum AI. Increased sensitivity of the microsomal oxidation of ethanol to inhibition by pyrazole and 4-methylpyrazole after chronic ethanol treatment. Biochem Pharmacol. 1987;36:3277–83.CrossRefPubMedGoogle Scholar
  34. 34.
    Chow HH, Hutchaleelaha A, Mayersohn M. Inhibitory effect of 4-methylpyrazole on antipyrine clearance in rats. Life Sci. 1992;50:661–6.CrossRefPubMedGoogle Scholar
  35. 35.
    Feierman DE, Cederbaum AI. Interaction of pyrazole and 4-methylpyrazole with hepatic microsomes: effect on cytochrome P-450 content, microsomal oxidation of alcohols, and binding spectra. Alcohol Clin Exp Res. 1985;9:421–8.CrossRefPubMedGoogle Scholar
  36. 36.
    Winters DK, Cederbaum AI. Time course characterization of the induction of cytochrome P-450 2E1 by pyrazole and 4-methylpyrazole. Biochim Biophys Acta. 1992;1117:15–24.CrossRefPubMedGoogle Scholar
  37. 37.
    Krikun G, Feierman DE, Cederbaum AI. Rat liver microsomal induction of the oxidation of drugs and alcohols, and sodium dodecyl sulfate-gel profiles after in vivo treatment with pyrazole or 4-methylpyrazole. J Pharmacol Exp Ther. 1986;237:1012–9.PubMedGoogle Scholar
  38. 38.
    McMartin KE, Sebastian CS, Dies D, Jacobsen D. Kinetics and metabolism of fomepizole in healthy humans. Clin Toxicol (Phila). 2012;50:375–83.CrossRefGoogle Scholar
  39. 39.
    Cederbaum AI, Berl L. Pyrazole and 4-methylpyrazole inhibit oxidation of ethanol and dimethyl sulfoxide by hydroxyl radicals generated from ascorbate, xanthine oxidase, and rat liver microsomes. Arch Biochem Biophys. 1982;216:530–43.CrossRefPubMedGoogle Scholar
  40. 40.
    Iaquinto G, Del Tacca M, Cuccurullo L, Parodi MC, Giardullo N, D’Onofrio V, Natale G, Carignani D, Ferraraccio F, Szabo S. Gastroprotection by 4-methylpyrazole against ethanol in humans. Dig Dis Sci. 1998;43:816–25.CrossRefPubMedGoogle Scholar
  41. 41.
    Marraffa J, Forrest A, Grant W, Stork C, McMartin K, Howland MA. Oral administration of fomepizole produces similar blood levels as identical intravenous dose. Clin Toxicol (Phila). 2008;46:181–6.CrossRefGoogle Scholar
  42. 42.
    Mayersohn M, Owens SM, Anaya AL, Bliss M, Achari R. 4-Methylpyrazole disposition in the dog: evidence for saturable elimination. J Pharm Sci. 1985;74:895–6.CrossRefPubMedGoogle Scholar
  43. 43.
    McMartin KE, Collins TD. Distribution of oral 4-methylpyrazole in the rat: inhibition of elimination by ethanol. J Toxicol Clin Toxicol. 1988;26:451–66.CrossRefPubMedGoogle Scholar
  44. 44.
    Murphy RC, Watkins WD. Pharmacology of pyrazoles. I. Structure elucidation of metabolites of 4-methylpyrazole. Biochem Biophys Res Commun. 1972;49:283–91.CrossRefPubMedGoogle Scholar
  45. 45.
    Hovda KE, Mundal H, Urdal P, McMartin K, Jacobsen D. Extremely slow formate elimination in severe methanol poisoning: a fatal case report. Clin Toxicol (Phila). 2007;45:516–21.CrossRefGoogle Scholar
  46. 46.
    Vu BD, Crouzier C, Hubert I, Galliot M, Baud FJ, Bourdon R. Etude analytique et pharmacocinetique du 4-methylpyrazole, nouvel antidote pour le traitement de l’intoxication a l’ethylene glycol. Ann Fais Exp Chim. 1992;85:99–110.Google Scholar
  47. 47.
    Jacobsen D, Ostensen J, Bredesen L, Ullstein E, McMartin K. 4-Methylpyrazole (4-MP) is effectively removed by haemodialysis in the pig model. Hum Exp Toxicol. 1996;15:494–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Jobard E, Harry P, Turcant A, Roy PM, Allain P. 4-Methylpyrazole and hemodialysis in ethylene glycol poisoning. J Toxicol Clin Toxicol. 1996;34:373–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Faessel H, Houze P, Baud FJ, Scherrmann JM. 4-methylpyrazole monitoring during haemodialysis of ethylene glycol intoxicated patients. Eur J Clin Pharmacol. 1995;49:211–3.CrossRefPubMedGoogle Scholar
  50. 50.
    McMartin KE, Jacobsen D, Hovda KE. Antidotes for poisoning by alcohols that form toxic metabolites. Brit J Clin Pharmacol 2016;81:505–515.Google Scholar
  51. 51.
    Hovda KE, Urdal P, Jacobsen D. Increased serum formate in the diagnosis of methanol poisoning. J Anal Toxicol. 2005;29:586–8.CrossRefPubMedGoogle Scholar
  52. 52.
    Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA, American Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol P. American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning. J Toxicol Clin Toxicol. 2002;40:415–46.CrossRefPubMedGoogle Scholar
  53. 53.
    Brent J. Fomepizole for ethylene glycol and methanol poisoning. N Engl J Med. 2009;360:2216–23.CrossRefPubMedGoogle Scholar
  54. 54.
    Megarbane B, Borron SW, Baud FJ. Current recommendations for treatment of severe toxic alcohol poisonings. Intensive Care Med. 2005;31:189–95.CrossRefPubMedGoogle Scholar
  55. 55.
    Hovda KE, Jacobsen D. Expert opinion: fomepizole may ameliorate the need for hemodialysis in methanol poisoning. Hum Exp Toxicol. 2008;27:539–46.CrossRefPubMedGoogle Scholar
  56. 56.
    Hovda KE, Froyshov S, Gudmundsdottir H, Rudberg N, Jacobsen D. Fomepizole may change the indication for HD in methanol poisoning: prospective study in 7 cases. Clin Nephrol. 2005;64:190–7.CrossRefPubMedGoogle Scholar
  57. 57.
    Buchanan JA, Alhelail M, Cetaruk EW, Schaeffer TH, Palmer RB, Kulig K, Brent J. Massive ethylene glycol ingestion treated with fomepizole alone-a viable therapeutic option. J Med Toxicol. 2010;6:131–4.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Ahmed A, Tschetter PA, Krasowski MD, Engelman A. Massive ethylene glycol poisoning triggers osmotic demyelination syndrome. J Emerg Med. 2014;46:e69–74.CrossRefPubMedGoogle Scholar
  59. 59.
    Roberts DM, Yates C, Megarbane B, Winchester JF, Maclaren R, Gosselin S, Nolin TD, Lavergne V, Hoffman RS, Ghannoum M. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Crit Care Med. 2015;43:461–72.CrossRefPubMedGoogle Scholar
  60. 60.
    Besenhofer LM, Adegboyega PA, Bartels M, Filary MJ, Perala AW, McLaren MC, McMartin KE. Inhibition of metabolism of diethylene glycol prevents target organ toxicity in rats. Toxicol Sci. 2010;117:25–35.CrossRefPubMedGoogle Scholar
  61. 61.
    Brophy PD, Tenenbein M, Gardner J, Bunchman TE, Smoyer WE. Childhood diethylene glycol poisoning treated with alcohol dehydrogenase inhibitor fomepizole and hemodialysis. Am J Kidney Dis. 2000;35:958–62.CrossRefPubMedGoogle Scholar
  62. 62.
    Borron SW, Baud FJ, Garnier R. Intravenous 4-methylpyrazole as an antidote for diethylene glycol and triethylene glycol poisoning: a case report. Vet Hum Toxicol. 1997;39:26–8.PubMedGoogle Scholar
  63. 63.
    Rollins YD, Filley CM, McNutt JT, Chahal S, Kleinschmidt-DeMasters BK. Fulminant ascending paralysis as a delayed sequela of diethylene glycol (Sterno) ingestion. Neurology. 2002;59:1460–3.CrossRefPubMedGoogle Scholar
  64. 64.
    Paasma R, Hovda KE, Hassanian-Moghaddam H, Brahmi N, Afshari R, Sandvik L, Jacobsen D. Risk factors related to poor outcome after methanol poisoning and the relation between outcome and antidotes--a multicenter study. Clin Toxicol (Phila). 2012;50:823–31.CrossRefGoogle Scholar
  65. 65.
    Zakharov S, Pelclova D, Urban P, Navratil T, Diblik P, Kuthan P, Hubacek JA, Miovsky M, Klempir J, Vaneckova M, Seidl Z, Pilin A, Fenclova Z, Petrik V, Kotikova K, Nurieva O, Ridzon P, Rulisek J, Komarc M, Hovda KE. Czech mass methanol outbreak 2012: epidemiology, challenges and clinical features. Clin Toxicol (Phila). 2014;52:1013–24.CrossRefGoogle Scholar
  66. 66.
    Hantson P, Wittebole X, Haufroid V. Ethanol therapy for methanol poisoning: duration and problems. Eur J Emerg Med. 2002;9:278–9.CrossRefPubMedGoogle Scholar
  67. 67.
    Zakharov S, Navratil T, Salek T, Kurcova I, Pelclova D. Fluctuations in serum ethanol concentration in the treatment of acute methanol poisoning: a prospective study of 21 patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2015;159:505–515.Google Scholar
  68. 68.
    Paasma R, Hovda KE, Tikkerberi A, Jacobsen D. Methanol mass poisoning in Estonia: outbreak in 154 patients. Clin Toxicol (Phila). 2007;45:152–7.CrossRefGoogle Scholar
  69. 69.
    Lepik KJ, Levy AR, Sobolev BG, Purssell RA, DeWitt CR, Erhardt GD, Kennedy JR, Daws DE, Brignall JL. Adverse drug events associated with the antidotes for methanol and ethylene glycol poisoning: a comparison of ethanol and fomepizole. Ann Emerg Med. 2009;53:439–50.CrossRefPubMedGoogle Scholar
  70. 70.
    Lepik KJ, Sobolev BG, Levy AR, Purssell RA, Dewitt CR, Erhardt GD, Baker JL, Kennedy JR, Daws DE. Medication errors associated with the use of ethanol and fomepizole as antidotes for methanol and ethylene glycol poisoning. Clin Toxicol (Phila). 2011;49:391–401.CrossRefGoogle Scholar
  71. 71.
    Caravati EM, Heileson HL, Jones M. Treatment of severe pediatric ethylene glycol intoxication without hemodialysis. J Toxicol Clin Toxicol. 2004;42:255–9.CrossRefPubMedGoogle Scholar
  72. 72.
    Sivilotti ML. Ethanol: tastes great! Fomepizole: less filling! Ann Emerg Med. 2009;53:451–3.CrossRefPubMedGoogle Scholar
  73. 73.
    Beatty L, Green R, Magee K, Zed P. A systematic review of ethanol and fomepizole use in toxic alcohol ingestions. Emerg Med Int. 2013;2013:638057.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Harry P, Jobard E, Briand M, Caubet A, Turcant A. Ethylene glycol poisoning in a child treated with 4-methylpyrazole. Pediatrics. 1998;102:E31.CrossRefPubMedGoogle Scholar
  75. 75.
    Baum CR, Langman CB, Oker EE, Goldstein CA, Aviles SR, Makar JK. Fomepizole treatment of ethylene glycol poisoning in an infant. Pediatrics. 2000;106:1489–91.CrossRefPubMedGoogle Scholar
  76. 76.
    Brown MJ, Shannon MW, Woolf A, Boyer EW. Childhood methanol ingestion treated with fomepizole and hemodialysis. Pediatrics. 2001;108:E77.CrossRefPubMedGoogle Scholar
  77. 77.
    Detaille T, Wallemacq P, de Clement CS, Vanbinst R, Dembour G, Hantson P. Fomepizole alone for severe infant ethylene glycol poisoning. Pediatr Crit Care Med. 2004;5:490–1.CrossRefPubMedGoogle Scholar
  78. 78.
    Gracia R, Latimer B, McMartin KE. Kinetics of fomepizole in pregnant rats. Clin Toxicol (Phila). 2012;50:743–8.CrossRefGoogle Scholar
  79. 79.
    Velez LI, Kulstad E, Shepherd G, Roth B. Inhalational methanol toxicity in pregnancy treated twice with fomepizole. Vet Hum Toxicol. 2003;45:28–30.PubMedGoogle Scholar
  80. 80.
    Feierman DE, Cederbaum AI. Increased content of cytochrome P-450 and 4-methylpyrazole binding spectrum after 4-methylpyrazole treatment. Biochem Biophys Res Commun. 1985;126:1076–81.CrossRefPubMedGoogle Scholar
  81. 81.
    Magnusson G, Nyberg JA, Bodin NO, Hansson E. Toxicity of pyrazole and 4-methylpyrazole in mice and rats. Experientia. 1972;28:1198–200.CrossRefPubMedGoogle Scholar
  82. 82.
    Blomstrand R, Ingemansson SO, Jensen M, Hedstrom CG. Normal electroretinogram and no toxicity signs after chronic and acute administration of the alcohol dehydrogenase inhibitor 4-methylpyrazole to the cynomolgus monkey (Macaca fascicularis)--a possible new treatment of methanol poisoning. Drug Alcohol Depend. 1984;13:9–20.CrossRefPubMedGoogle Scholar
  83. 83.
    Lindros KO, Stowell L, Vaananen H, Sipponen P, Lamminsivu U, Pikkarainen P, Salaspuro M. Uninterrupted prolonged ethanol oxidation as a main pathogenetic factor of alcoholic liver damage: evidence from a new liquid diet animal model. Liver. 1983;3:79–91.CrossRefPubMedGoogle Scholar
  84. 84.
    MacDonald E. Effect of pyrazole, 4-methylpyrazole, 4-bromopyrazole and 4-iodopyrazole on brain noradrenaline levels of mice and rats. Acta Pharmacol Toxicol (Copenh). 1976;39:513–24.CrossRefGoogle Scholar
  85. 85.
    Blomstrand R, Theorell H. Inhibitory effect on ethanol oxidation in man after administration of 4-methylpyrazole. Life Sci II. 1970;9:631–40.CrossRefPubMedGoogle Scholar
  86. 86.
    Salaspuro MP, Lindros KO, Pikkarainen PH. Effect of 4-methylpyrazole on ethanol elimination rate and hepatic redox changes in alcoholics with adequate or inadequate nutrition and in nonalcoholic controls. Metabolism. 1978;27:631–9.CrossRefPubMedGoogle Scholar
  87. 87.
    Kupari M, Lindros K, Hillbom M, Heikkila J, Ylikahri R. Cardiovascular effects of acetaldehyde accumulation after ethanol ingestion: their modification by beta-adrenergic blockade and alcohol dehydrogenase inhibition. Alcohol Clin Exp Res. 1983;7:283–8.CrossRefPubMedGoogle Scholar
  88. 88.
    Borron SW, Megarbane B, Baud FJ. Fomepizole in treatment of uncomplicated ethylene glycol poisoning. Lancet. 1999;354:831.CrossRefPubMedGoogle Scholar
  89. 89.
    Megarbane B, Borron SW, Trout H, Hantson P, Jaeger A, Krencker E, Bismuth C, Baud FJ. Treatment of acute methanol poisoning with fomepizole. Intensive Care Med. 2001;27:1370–8.CrossRefPubMedGoogle Scholar
  90. 90.
    Zakharov S, Pelclova D, Navratil T, Belacek J, Kurcova I, Komzak O, Salek T, Latta J, Turek R, Bocek R, Kucera C, Hubacek JA, Fenclova Z, Petrik V, Cermak M, Hovda KE. Intermittent hemodialysis is superior to continuous veno-venous hemodialysis/hemodiafiltration to eliminate methanol and formate during treatment for methanol poisoning. Kidney Int. 2014;86:199–207.CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Antizol® (fomepizole) Product Monograph. Minnetonka: Orphan Medical Inc; 2001.Google Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Pharmacology, Toxicology & NeuroscienceLouisiana State University Health Sciences Center - ShreveportShreveportUSA
  2. 2.The Norwegian CBRNE Centre of Medicine, Department of Acute Medicine, Medical DivisionOslo University HospitalOsloNorway
  3. 3.Department of Acute Medicine, Division of MedicineOslo University HospitalOsloNorway

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