Display options
Cite
Kalsi SS, Wood DM, Waring WS, et al. Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?. Open Access Emerg Med. 2011;3:69-76doi: 10.2147/OAEM.S24962.
Kalsi, S. S., Wood, D. M., Waring, W. S., & Dargan, P. I. (2011). Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?. Open access emergency medicine : OAEM, 369-76. https://doi.org/10.2147/OAEM.S24962
Kalsi, Sarbjeet S, et al. "Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?." Open access emergency medicine : OAEM vol. 3 (2011): 69-76. doi: https://doi.org/10.2147/OAEM.S24962
Kalsi SS, Wood DM, Waring WS, Dargan PI. Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?. Open Access Emerg Med. 2011 Oct 13;3:69-76. doi: 10.2147/OAEM.S24962. eCollection 2011. PMID: 27147854; PMCID: PMC4753969.
Copy Download .nbib Format: NLM
Share it on

Open Access Emerg Med. 2011 Oct 13;3:69-76. doi: 10.2147/OAEM.S24962. eCollection 2011.

Does cytochrome P450 liver isoenzyme induction increase the risk of liver toxicity after paracetamol overdose?.

Open access emergency medicine : OAEM

Sarbjeet S Kalsi, David M Wood, W Stephen Waring, Paul I Dargan

Affiliations

  1. Emergency Department, Guy's and St Thomas' NHS Foundation Trust, London;; Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London;
  2. Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London;
  3. York Teaching Hospital NHS Foundation Trust, York, UK.

PMID: 27147854 PMCID: PMC4753969 DOI: 10.2147/OAEM.S24962

Abstract

Paracetamol (acetaminophen, N-acetyl-p-aminophenol, 4-hydroxyacetanilide) is the most common cause of acute liver failure in developed countries. There are a number of factors which potentially impact on the risk of an individual developing hepatotoxicity following an acute paracetamol overdose. These include the dose of paracetamol ingested, time to presentation, decreased liver glutathione, and induction of cytochrome P450 (CYP) isoenzymes responsible for the metabolism of paracetamol to its toxic metabolite N-acetyl-p-benzoquinoneimine (NAPQI). In this paper, we review the currently published literature to determine whether induction of relevant CYP isoenzymes is a risk factor for hepatotoxicity in patients with acute paracetamol overdose. Animal and human in vitro studies have shown that the CYP isoenzyme responsible for the majority of human biotransformation of paracetamol to NAPQI is CYP2E1 at both therapeutic and toxic doses of paracetamol. Current UK treatment guidelines suggest that patients who use a number of drugs therapeutically should be treated as "high-risk" after paracetamol overdose. However, based on our review of the available literature, it appears that the only drugs for which there is evidence of the potential for an increased risk of hepatotoxicity associated with paracetamol overdose are phenobarbital, primidone, isoniazid, and perhaps St John's wort. There is no evidence that other drugs often quoted as increasing risk, such as carbamazepine, phenytoin, primidone, rifampicin, rifabutin, efavirenz, or nevirapine, should be considered risk factors for hepatotoxicity in patients presenting with acute paracetamol overdose.

Keywords: hepatotoxicity; isoenzymes; overdose; paracetamol

References

  1. Drug Metab Dispos. 1997 Oct;25(10):1165-75 - PubMed
  2. Lancet. 1990 Jun 23;335(8704):1526 - PubMed
  3. Clin Pharmacol Ther. 2000 Mar;67(3):275-82 - PubMed
  4. Pharmacology. 1974;12 (3):129-43 - PubMed
  5. Chem Res Toxicol. 2006 May;19(5):701-9 - PubMed
  6. QJM. 2008 Feb;101(2):121-5 - PubMed
  7. Biopharm Drug Dispos. 1999 Sep;20(6):285-91 - PubMed
  8. J Pharmacol Exp Ther. 1973 Oct;187(1):185-94 - PubMed
  9. Br Med J. 1966 Aug 27;2(5512):497-9 - PubMed
  10. Pediatrics. 1975 Jun;55(6):871-6 - PubMed
  11. Ugeskr Laeger. 1995 Feb 13;157(7):899-900 - PubMed
  12. Clin Pharmacol Ther. 1997 Jul;62(1):21-8 - PubMed
  13. Liver Transpl. 2002 Nov;8(11):1055-62 - PubMed
  14. Lancet. 1975 Sep 27;2(7935):579-81 - PubMed
  15. Drug Metab Dispos. 2003 Mar;31(3):282-8 - PubMed
  16. Hepatology. 2005 Dec;42(6):1364-72 - PubMed
  17. Toxicol Appl Pharmacol. 1998 Sep;152(1):193-9 - PubMed
  18. Drug Metab Rev. 2011 Feb;43(1):41-52 - PubMed
  19. Br J Clin Pharmacol. 1981 Aug;12(2):149-53 - PubMed
  20. Br J Clin Pharmacol. 2004 Apr;57(4):495-9 - PubMed
  21. Antimicrob Agents Chemother. 1997 May;41(5):924-6 - PubMed
  22. Xenobiotica. 2009 Jan;39(1):11-21 - PubMed
  23. Clin Pharmacol Ther. 1974 Oct;16(4):676-84 - PubMed
  24. Clin Pharmacol Ther. 1993 Aug;54(2):142-9 - PubMed
  25. Clin Pharmacol Ther. 2002 Sep;72(3):276-87 - PubMed
  26. Lancet. 1995 Aug 26;346(8974):547-52 - PubMed
  27. J Pharmacol Exp Ther. 1987 Nov;243(2):565-70 - PubMed
  28. Drug Metab Lett. 2010 Dec;4(4):185-94 - PubMed
  29. BMJ. 1990 Oct 27;301(6758):964-6 - PubMed
  30. J Hepatol. 2009 Feb;50(2):306-13 - PubMed
  31. Clin Pharmacol Ther. 1997 Jan;61(1):24-34 - PubMed
  32. Emerg Med J. 2002 May;19(3):202-5 - PubMed
  33. Dig Dis Sci. 2005 Oct;50(10):1836-8 - PubMed
  34. Med J Aust. 2008 Mar 3;188(5):296-301 - PubMed
  35. J Toxicol Clin Toxicol. 1999;37(6):753-7 - PubMed
  36. Pharmacology. 1985;30(2):100-8 - PubMed
  37. Lancet. 1971 Mar 13;1(7698):519-22 - PubMed
  38. Dig Dis Sci. 2007 Jan;52(1):208-9 - PubMed
  39. Clin Pharmacol Ther. 2001 Oct;70(4):317-26 - PubMed
  40. Pharmacology. 1974;12(4-5):251-71 - PubMed
  41. J Gastroenterol Hepatol. 1999 Aug;14(8):817-21 - PubMed
  42. J Pharm Pharmacol. 1968 Jan;20(1):64-7 - PubMed
  43. Biochem Biophys Res Commun. 1994 Aug 30;203(1):532-9 - PubMed
  44. Biochem Pharmacol. 1993 Apr 22;45(8):1563-9 - PubMed
  45. Curr Drug Metab. 2010 Mar;11(3):276-82 - PubMed
  46. Eur J Clin Pharmacol. 1996;50(5):411-5 - PubMed
  47. Can J Gastroenterol. 2002 Oct;16(10):672-6 - PubMed
  48. Drug Metab Dispos. 2007 Jul;35(7):1223-31 - PubMed
  49. Biochem Biophys Res Commun. 2002 Mar 8;291(4):1089-94 - PubMed
  50. Chem Res Toxicol. 1998 Apr;11(4):295-301 - PubMed
  51. Hum Exp Toxicol. 1992 Jul;11(4):265-70 - PubMed
  52. Ann Intern Med. 2002 Dec 17;137(12):947-54 - PubMed
  53. J Pharmacol Exp Ther. 1987 Feb;240(2):578-83 - PubMed
  54. Drugs. 1983 Mar;25(3):290-314 - PubMed
  55. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1327-31 - PubMed
  56. Hum Toxicol. 1988 Jan;7(1):33-4 - PubMed
  57. Toxicol Sci. 2005 Sep;87(1):146-55 - PubMed
  58. Cochrane Database Syst Rev. 2006 Apr 19;(2):CD003328 - PubMed
  59. Aliment Pharmacol Ther. 1993 Oct;7(5):477-85 - PubMed
  60. JAMA. 2003 Sep 17;290(11):1500-4 - PubMed
  61. Ann Intern Med. 1984 Sep;101(3):403 - PubMed
  62. Br J Clin Pharmacol. 1979 Feb;7(2):201-6 - PubMed
  63. J Clin Pharmacol. 2004 Nov;44(11):1273-81 - PubMed
  64. Br Med J. 1966 Aug 27;2(5512):506-7 - PubMed
  65. Drug Metab Dispos. 2000 Dec;28(12):1397-400 - PubMed
  66. J Pharmacol Exp Ther. 1973 Oct;187(1):203-10 - PubMed
  67. Arch Biochem Biophys. 1989 Jun;271(2):270-83 - PubMed
  68. Mol Pharmacol. 1980 Nov;18(3):536-42 - PubMed
  69. Ugeskr Laeger. 1996 Nov 25;158(48):6892-5 - PubMed
  70. Gut. 1975 Oct;16(10):838 - PubMed
  71. Ann Emerg Med. 2007 Sep;50(3):292-313 - PubMed
  72. Drug Metab Dispos. 2009 Aug;37(8):1611-21 - PubMed
  73. Gastroenterology. 1989 Aug;97(2):439-45 - PubMed
  74. J Med Chem. 1982 Aug;25(8):885-6 - PubMed
  75. Drug Metab Dispos. 2002 Jul;30(7):795-804 - PubMed
  76. J Pharmacol Exp Ther. 1973 Oct;187(1):211-7 - PubMed

Publication Types