Are some people at increased risk of paracetamol-induced liver injury? A critical review of the literature

European Journal of Clinical Pharmacology

Volumn 74, Issue 2, 2018, Pages 147-160

  Caparrotta, Thomas M ^a   Antoine, Daniel J ^b   Dear, James W ^c  

^a NHS LOTHIAN   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Acetaminophen; DILI; Genomics; Hepatotoxicity; Paracetamol

Indexed keywords

CYTOCHROME P450; GLUCURONOSYLTRANSFERASE; GLUTATHIONE TRANSFERASE; HERMES ANTIGEN; PARACETAMOL; SULFOTRANSFERASE; ANALGESIC AGENT;

AGE; ALCOHOL CONSUMPTION; BODY WEIGHT; CHRONIC LIVER DISEASE; DRUG BIOAVAILABILITY; DRUG INTERACTION; DRUG METABOLISM; DRUG OVERDOSE; DRUG TOXICITY; ENZYME INDUCTION; ENZYME INHIBITION; ENZYME POLYMORPHISM; ETHNICITY; GENETIC DIFFERENCE; GENETIC HETEROGENEITY; GENETIC POLYMORPHISM; GILBERT DISEASE; HUMAN; LIVER INJURY; LIVER TOXICITY; MALNUTRITION; MAXIMUM PLASMA CONCENTRATION; MORTALITY; NUTRITIONAL STATUS; PHARMACOKINETICS; RANDOMIZED CONTROLLED TRIAL (TOPIC); RETROSPECTIVE STUDY; REVIEW; RISK FACTOR; SYSTEMATIC REVIEW; TOXIC HEPATITIS;

ACETAMINOPHEN; ANALGESICS, NON-NARCOTIC; CHEMICAL AND DRUG INDUCED LIVER INJURY; HUMANS; RISK FACTORS;

EID: 85032008416     PISSN: 00316970     EISSN: 14321041     Source Type: Journal    
DOI: 10.1007/s00228-017-2356-6     Document Type: Review

References (137)

1. Ward B, Alexander-Williams JM (1999) Paracetamol revisited: a review of the pharmacokinetics and pharmacodynamics. Acute Pain 2:139–149
2. Bateman DN, Carroll R, Pettie J, Yamamoto T, Elamin MEMO, Peart L et al (2014) Effect of the UK’s revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment. Br J Clin Pharmacol 78:610–618
3. Prescott LF, Illingworth RN, Critchley JA, Stewart MJ, Adam RD, Proudfoot AT (1979) Intravenous N-acetylcystine: the treatment of choice for paracetamol poisoning. Br Med J 2:1097–1100
4. Townsend E, Hawton K, Harriss L, Bale E, Bond A (2001) Substances used in deliberate self-poisoning 1985-1997: trends and associations with age, gender, repetition and suicide intent. Soc Psychiatry Psychiatr Epidemiol 36:228–234
5. Mowry JB, Spyker DA, Cantilena LR, McMillan N, Ford M (2014) 2013 annual report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 31st annual report. Clin Toxicol Phila Pa 52:1032–1283
6. Vitols S (2003) Paracetamol hepatotoxicity at therapeutic doses. J Intern Med 253:95–98
7. Dart RC, Bailey E (2007) Does therapeutic use of acetaminophen cause acute liver failure? Pharmacother J Hum Pharmacol Drug Ther 27:1219–1230
8. Craig DGN, Bates CM, Davidson JS, Martin KG, Hayes PC, Simpson KJ (2012) Staggered overdose pattern and delay to hospital presentation are associated with adverse outcomes following paracetamol-induced hepatotoxicity. Br J Clin Pharmacol 73:285–294
9. Ferner RE, Dear JW, Bateman DN (2011) Management of paracetamol poisoning. BMJ 342:d2218
10. Medicines and Healthcare products Regulatory Agency (MHRA) www mhra gov uk. Paracetamol overdose: Simplification of the use of intravenous acetylcysteine. http://webarchive.nationalarchives.gov.uk/content/20141205150130/http://www.mhra.gov.uk/Safetyinformation/Safetywarningsalertsandrecalls/Safetywarningsandmessagesformedicines/CON178225 (accessed 19 Dec 2016)
11. Bannwarth B, Pehourcq F, Lagrange F, Matoga M, Maury S, Palisson M et al (2001) Single and multiple dose pharmacokinetics of acetaminophen (paracetamol) in polymedicated very old patients with rheumatic pain. J Rheumatol 28:182–184
12. Kobrinsky NL, Hartfield D, Horner H, Maksymiuk A, Minuk GY, White DF et al (1996) Treatment of advanced malignancies with high-dose acetaminophen and N-acetylcysteine rescue. Cancer Investig 14:202–210
13. Prescott LF (1980) Kinetics and metabolism of paracetamol and phenacetin. Br J Clin Pharmacol 10(Suppl 2):291S–298S
14. Rawlins MD, Henderson DB, Hijab AR (1977) Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration. Eur J Clin Pharmacol 11:283–286
15. Penna A, Buchanan N (1991) Paracetamol poisoning in children and hepatotoxicity. Br J Clin Pharmacol 32:143–149
16. Rumack BH (2004) Acetaminophen misconceptions. Hepatology 40:10–15
17. Zhao L, Pickering G (2011) Paracetamol metabolism and related genetic differences. Drug Metab Rev 43:41–52
18. Manyike PT, Kharasch ED, Kalhorn TF, Slattery JT (2000) Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clin Pharmacol Ther 67:275–282
19. Sarich T, Kalhorn T, Magee S, Al-Sayegh F, Adams S, Slattery J et al (1997) The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin. Clin Pharmacol Ther 62:21–28
20. McGill MR, Jaeschke H (2013) Metabolism and disposition of acetaminophen: recent advances in relation to hepatotoxicity and diagnosis. Pharm Res 30:2174–2187
21. Mitchell JR, Jollow DJ, Potter WZ, Davis DC, Gillette JR, Brodie BB (1973) Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. J Pharmacol Exp Ther 187:185–194
22. Brune K, Renner B, Tiegs G (2015) Acetaminophen/paracetamol: a history of errors, failures and false decisions. Eur J Pain 19:953–965
23. Heard K, Green JL, Anderson V, Bucher-Bartelson B, Dart RC (2016) Paracetamol (acetaminophen) protein adduct concentrations during therapeutic dosing. Br J Clin Pharmacol 81:562–568
24. Watkins PB, Kaplowitz N, Slattery JT, Colonese CR, Colucci SV, Stewart PW et al (2006) Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial. JAMA 296:87–93
25. Heard K, Green JL, Anderson V, Bucher-Bartelson B, Dart RC (2014) A randomized, placebo-controlled trial to determine the course of aminotransferase elevation during prolonged acetaminophen administration. BMC Pharmacol Toxicol 15:39
26. Gulmez SE, Larrey D, Pageaux G-P, Lignot S, Lassalle R, Jové J et al (2013) Transplantation for acute liver failure in patients exposed to NSAIDs or paracetamol (acetaminophen). Drug Saf 36:135–144
27. Critchley JA, Nimmo GR, Gregson CA, Woolhouse NM, Prescott LF (1986) Inter-subject and ethnic differences in paracetamol metabolism. Br J Clin Pharmacol 22:649–657
28. Esteban A, Pérez-Mateo M (1999) Heterogeneity of paracetamol metabolism in Gilbert’s syndrome. Eur J Drug Metab Pharmacokinet 24:9–13
29. Ullrich D, Sieg A, Blume R, Bock KW, Schröter W, Bircher J (1987) Normal pathways for glucuronidation, sulphation and oxidation of paracetamol in Gilbert’s syndrome. Eur J Clin Investig 17:237–240
30. Bock KW (2010) Functions and transcriptional regulation of adult human hepatic UDP-glucuronosyl-transferases (UGTs): mechanisms responsible for interindividual variation of UGT levels. Biochem Pharmacol 80:771–777
31. Bock KW, Forster A, Gschaidmeier H, Brück M, Münzel P, Schareck W et al (1993) Paracetamol glucuronidation by recombinant rat and human phenol UDP-glucuronosyltransferases. Biochem Pharmacol 45:1809–1814
32. Court MH, Freytsis M, Wang X, Peter I, Guillemette C, Hazarika S et al (2013) The UDP-glucuronosyltransferase (UGT) 1A polymorphism c.2042C>G (rs8330) is associated with increased human liver acetaminophen glucuronidation, increased UGT1A exon 5a/5b splice variant mRNA ratio, and decreased risk of unintentional acetaminophen-induced acute liver failure. J Pharmacol Exp Ther 345:297–307
33. de Morais SM, Uetrecht JP, Wells PG (1992) Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert’s syndrome. Gastroenterology 102:577–586
34. Douglas AP, Savage RL, Rawlins MD (1978) Paracetamol (acetaminophen) kinetics in patients with Gilbert’s syndrome. Eur J Clin Pharmacol 13:209–212
35. Coughtrie MWH (2002) Sulfation through the looking glass—recent advances in sulfotransferase research for the curious. Pharmacogenomics J 2:297–308
36. Raftogianis RB, Wood TC, Otterness DM, Van Loon JA, Weinshilboum RM (1997) Phenol sulfotransferase pharmacogenetics in humans: association of commonSULT1A1alleles with TS PST phenotype. Biochem Biophys Res Commun 239:298–304
37. Tanaka E, Terada MS (2000) Cytochrome P450 2E1: its clinical and toxicological role. J Clin Pharm Ther 25:165–175
38. Zhou Y, Ingelman-Sundberg, M, Lauschke, V Worldwide distribution of cytochrome P450 alleles: a meta-analysis of population-scale sequencing projects. Clin Pharmacol Ther; [Accessed June 2017]
39. Court MH, Peter I, Hazarika S, Vasiadi M, Greenblatt DJ, Lee WM et al (2013) Candidate gene polymorphisms in patients with acetaminophen-induced acute liver failure. Drug Metab Dispos 42:28–32
40. Coles B, Wilson I, Wardman P, Hinson JA, Nelson SD, Ketterer B (1988) The spontaneous and enzymatic reaction of N-acetyl-p-benzoquinonimine with glutathione: a stopped-flow kinetic study. Arch Biochem Biophys 264:253–260
41. Eaton DL, Bammler TK (1999) Concise review of the glutathione S-transferases and their significance to toxicology. Toxicol Sci 49:156–164
42. Harrill AH, Watkins PB, Su S, Ross PK, Harbourt DE, Stylianou IM et al (2009) Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res 19:1507–1515
43. Tujios S, Fontana RJ (2011) Mechanisms of drug-induced liver injury: from bedside to bench. Nat Rev Gastroenterol Hepatol 8:202–211
44. Miller RP, Roberts RJ, Fischer LJ (1976) Acetaminophen elimination kinetics in neonates, children, and adults. Clin Pharmacol Ther 19:284–294
45. Alam SN, Roberts RJ, Fischer LJ (1977) Age-related differences in salicylamide and acetaminophen conjugation in man. J Pediatr 90:130–135
46. van der Marel CD, Anderson BJ, van Lingen RA, Holford NHG, Pluim MAL, Jansman FGA et al (2003) Paracetamol and metabolite pharmacokinetics in infants. Eur J Clin Pharmacol 59:243–251
47. van Lingen RA, Deinum J, Quak J, Kuizenga A, van Dam JG, Anand K et al (1999) Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates. Arch Dis Child Fetal Neonatal Ed 80:F59–F63
48. Nahata MC, Powell DA, Durrell DE, Miller MA (1984) Acetaminophen accumulation in pediatric patients after repeated therapeutic doses. Eur J Clin Pharmacol 27:57–59
49. Arana A, Morton NS, Hansen TG (2001) Treatment with paracetamol in infants. Acta Anaesthesiol Scand 45:20–29
50. Roberts I, Robinson MJ, Mughal MZ, Ratcliffe JG, Prescott LF (1984) Paracetamol metabolites in the neonate following maternal overdose. Br J Clin Pharmacol 18:201–206
51. Lieh-Lai MW, Sarnaik AP, Newton JF, Miceli JN, Fleischmann LE, Hook JB et al (1984) Metabolism and pharmacokinetics of acetaminophen in a severely poisoned young child. J Pediatr 105:125–128
52. Peterson RG, Rumack BH (1981) Age as a variable in acetaminophen overdose. Arch Intern Med 141:390–393
53. Meredith TJ, Newman B, Goulding R (1978) Paracetamol poisoning in children. Br Med J 2:478–479
54. Rumack BH (1984) Acetaminophen overdose in young children. Treatment and effects of alcohol and other additional ingestants in 417 cases. Am J Dis Child 1960 138:428–433
55. Veltri JC, Rollins DE (1988) A comparison of the frequency and severity of poisoning cases for ingestion of acetaminophen, aspirin, and ibuprofen. Am J Emerg Med 6:104–107
56. Rivera-Penera T, Gugig R, Davis J, McDiarmid S, Vargas J, Rosenthal P et al (1997) Outcome of acetaminophen overdose in pediatric patients and factors contributing to hepatotoxicity. J Pediatr 130:300–304
57. Heubi JE, Barbacci MB, Zimmerman HJ (1998) Therapeutic misadventures with acetaminophen: hepatoxicity after multiple doses in children. J Pediatr 132:22–27
58. Anderson BJ (1998) What we don’t know about paracetamol in children. Paediatr Anaesth 8:451–460
59. Bond GR (2004) Reduced toxicity of acetaminophen in children: it’s the liver. J Toxicol Clin Toxicol 42:149–152
60. Makin AJ, Wendon J, Williams R (1995) A 7-year experience of severe acetaminophen-induced hepatotoxicity (1987–1993). Gastroenterology 109:1907–1916
61. Schmidt LE (2005) Age and paracetamol self-poisoning. Gut 54:686–690
62. Briant RH, Dorrington RE, Cleal J, Williams FM (1976) The rate of acetaminophen metabolism in the elderly and the young. J Am Geriatr Soc 24:359–361
63. Triggs EJ, Nation RL, Long A, Ashley JJ (1975) Pharmacokinetics in the elderly. Eur J Clin Pharmacol 8:55–62
64. Fulton B, James O, Rawlins M (1979) The influence of age on the pharmacokinetics of paracetamol [proceedings]. Br J Clin Pharmacol; 7
65. Pickering G, Schneider E, Papet I, Pujos-Guillot E, Pereira B, Simen E et al (2011) Acetaminophen metabolism after major surgery: a greater challenge with increasing age. Clin Pharmacol Ther 90:707–711
66. Wynne HA, Cope LH, Herd B, Rawlins MD, James OF, Woodhouse KW (1990) The association of age and frailty with paracetamol conjugation in man. Age Ageing 19:419–424
67. Liukas A, Kuusniemi K, Aantaa R, Virolainen P, Niemi M, Neuvonen PJ et al (2011) Pharmacokinetics of intravenous paracetamol in elderly patients. Clin Pharmacokinet 50:121–129
68. Divoll M, Abernethy DR, Ameer B, Greenblatt DJ (1982) Acetaminophen kinetics in the elderly. Clin Pharmacol Ther 31:151–156
69. Miners JO, Penhall R, Robson RA, Birkett DJ (1988) Comparison of paracetamol metabolism in young adult and elderly males. Eur J Clin Pharmacol 35:157–160
70. Herd B, Wynne H, Wright P, James O, Woodhouse K (1991) The effect of age on glucuronidation and sulphation of paracetamol by human liver fractions. Br J Clin Pharmacol 32:768–770
71. Bannwarth B, Netter P, Lapicque F, Gillet P, Pere P, Boccard E et al (1992) Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol. Br J Clin Pharmacol 34:79–81
72. Mitchell SJ, Hilmer SN, Murnion BP, Matthews S (2011) Hepatotoxicity of therapeutic short-course paracetamol in hospital inpatients: impact of ageing and frailty. J Clin Pharm Ther 36:327–335
73. Whitcomb DC, Block GD (1994) Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA 272:1845–1850
74. Bolesta S, Haber SL (2002) Hepatotoxicity associated with chronic acetaminophen administration in patients without risk factors. Ann Pharmacother 36:331–333
75. Vale JA, Proudfoot AT (1995) Paracetamol (acetaminophen) poisoning. Lancet 346:547–552
76. Mitchell J, Jollow D, Potter W, Gillette J, Brodie B Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J Pharmacol Exp Ther 187:211–217
77. Mandl J, Bánhegyi G, Kalapos MP, Garzó T (1995) Increased oxidation and decreased conjugation of drugs in the liver caused by starvation. Altered metabolism of certain aromatic compounds and acetone. Chem Biol Interact 96:87–101
78. Kurtovic J, Riordan SM (2003) Paracetamol-induced hepatotoxicity at recommended dosage. J Intern Med 253:240–243
79. McClain CJ, Price S, Barve S, Devalarja R, Shedlofsky S (1999) Acetaminophen hepatotoxicity: an update. Curr Gastroenterol Rep 1:42–49
80. Eriksson LS, Broome U, Kalin M, Lindholm M (1992) Hepatotoxicity due to repeated intake of low doses of paracetamol. J Intern Med 231:567–570
81. Moling O, Cairon E, Rimenti G, Rizza F, Pristerá R, Mian P (2006) Severe hepatotoxicity after therapeutic doses of acetaminophen. Clin Ther 28:755–760
82. Rumack BH (2002) Acetaminophen hepatotoxicity: the first 35 years. J Toxicol Clin Toxicol 40:3–20
83. Schiødt FV, Rochling FA, Casey DL, Lee WM (1997) Acetaminophen toxicity in an urban county hospital. N Engl J Med 337:1112–1118
84. Lauterburg BH (2002) Analgesics and glutathione. Am J Ther 9:225
85. Lee TD, Sadda MR, Mendler MH, Bottiglieri T, Kanel G, Mato JM et al (2004) Abnormal hepatic methionine and glutathione metabolism in patients with alcoholic hepatitis. Alcohol Clin Exp Res 28:173–181
86. Joint Formulary Committee. British National Formulary. December 2016 ed. BMJ Group and Pharmaceuticle Press: London, 2016
87. Administration AGD of HTG. OTC medicine monograph: Paracetamol for oral use. Ther. Goods Adm. TGA. 2013.https://www.tga.gov.au/otc-medicine-monograph-paracetamol-oral-use (accessed 4 May 2017)
88. Research C for DE and. Drug Safety and Availability - Notice to Industry: Final Guidance for Over-the-Counter Products that Contain Acetaminophen https://www.fda.gov/Drugs/DrugSafety/ucm310469.htm (accessed 4 May 2017)
89. Dart RC, Rumack BH (2012) Intravenous acetaminophen in the United States: iatrogenic dosing errors. Pediatrics 129:349–353
90. Fatal accident inquiry into the death of Danielle Welsh—judgments & sentences—Judiciary of Scotland. http://www.scotland-judiciary.org.uk/10/715/Fatal-Accident-Inquiry-into-the-death-of-Danielle-Welsh (accessed 4 May 2017)
91. Claridge LC, Eksteen B, Smith A, Shah T, Holt AP (2010) Acute liver failure after administration of paracetamol at the maximum recommended daily dose in adults. BMJ 341:c6764
92. Pearce B, Grant IS (2008) Acute liver failure following therapeutic paracetamol administration in patients with muscular dystrophies. Anaesthesia 63:89–91
93. Temple AR, Benson GD, Zinsenheim JR, Schweinle JE (2006) Multicenter, randomized, double-blind, active-controlled, parallel-group trial of the long-term (6–12 months) safety of acetaminophen in adult patients with osteoarthritis. Clin Ther 28:222–235
94. Prescribing notes for acute pain. http://handbook.ggcmedicines.org.uk/guidelines/pain-post-operative-nausea-and-vomiting-and-palliative-care-symptoms/prescribing-notes-for-acute-pain/ (accessed 4 May 2017)
95. Zimmerman HJ, Maddrey WC (1995) Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. Hepatol Baltim Md 22:767–773
96. Black M (1984) Acetaminophen hepatotoxicity. Annu Rev Med 35:577–593
97. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB (1986) Acetaminophen hepatotoxicity in alcoholics: a therapeutic misadventure. Ann Intern Med 104:399
98. Wootton FT, Lee WM (1990) Acetaminophen hepatotoxicity in the alcoholic. ET J 83:1047–1049
99. Kumar S, Rex DK (1991) Failure of physicians to recognize acetaminophen hepatotoxicity in chronic alcoholics. Arch Intern Med 151:1189–1191
100. Riordan SM, Williams R (2002) Alcohol exposure and paracetamol-induced hepatotoxicity. Addict Biol 7:191–206
101. Draganov P, Durrence H, Cox C, Reuben A (2000) Alcohol-acetaminophen syndrome. Postgrad Med 107:189–195
102. Licht H, Seeff LB, Zimmerman HJ (1980) Apparent potentiation of acetaminophen hepatotoxicity by alcohol. Ann Intern Med 92:511–511
103. O’Dell JR, Zetterman RK, Burnett DA (1986) Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic. JAMA 255:2636–2637
104. Lauterburg B, Velez M (1988) Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut 29:1153–1157
105. Lesser PB, Vietti MM, Clark WD (1986) Lethal enhancement of therapeutic doses of acetaminophen by alcohol. Dig Dis Sci 31:103–105
106. Florén C-H, Thesleff P, Nilsson Å (1987) Severe liver damage caused by therapeutic doses of acetaminophen. Acta Med Scand 222:285–288
107. Johnston SC, Pelletier LL (1997) Enhanced hepatotoxicity of acetaminophen in the alcoholic patient. Two case reports and a review of the literature. Medicine (Baltimore) 76:185–191
108. Emby BN, Fraser DJ (1977) Hepatotoxicity of paracetamol enhanced by ingestion of alcohol—report of two cases. S Afr Med J 51:208–209
109. Tanaka E, Yamazaki K, Misawa S (2000) Update: the clinical importance of acetaminophen hepatotoxicity in non-alcoholic and alcoholic subjects. J Clin Pharm Ther 25:325–332
110. Thummel KE, Slattery JT, Ro H, Chien JY, Nelson SD, Lown KE et al (2000) Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults. Clin Pharmacol Ther 67:591–599
111. Banda P, Quart B (1982) The effect of mild alcohol consumption on the metabolism of acetaminophen in man. Res Commun Chem Pathol Pharmacol 38:57–70
112. Black M, Raucy J (1986) Acetaminophen, alcohol, and cytochrome P-450. Ann Intern Med 104:427–429
113. Kuffner EK, Dart RC, Bogdan GM, Hill RE, Casper E, Darton L (2001) Effect of maximal daily doses of acetaminophen on the liver of alcoholic patients: a randomized, double-blind, placebo-controlled trial. Arch Intern Med 161:2247–2252
114. Critchley JAJH, Scott AW, Dyson EH, Jarvie DR, Prescott LFI (1983) There a place for cimetidine or ethanol in the treatment of paracetamol poisoning? Lancet 321:1375–1376
115. Waring WS, Stephen AF, Malkowska AM, Robinson ODG (2008) Acute ethanol coingestion confers a lower risk of hepatotoxicity after deliberate acetaminophen overdose. Acad Emerg Med 15:54–58
116. Prescott LF (2000) Paracetamol, alcohol and the liver. Br J Clin Pharmacol 49:291–301
117. Dart RC, Kuffner EK, Rumack BH (2000) Treatment of pain or fever with paracetamol (acetaminophen) in the alcoholic patient: a systematic review. Am J Ther 7:123–134
118. Makin A, Williams R (2000) Paracetamol hepatotoxicity and alcohol consumption in deliberate and accidental overdose. QJM 93:341–349
119. Schiødt FV, Lee WM, Bondesen S, Ott P, Christensen E (2002) Influence of acute and chronic alcohol intake on the clinical course and outcome in acetaminophen overdose. Aliment Pharmacol Ther 16:707–715
120. Toes MJ, Jones AL, Prescott L (2005) Drug interactions with paracetamol. Am J Ther 12:56–66
121. Farrell G, Cooksley W, Powell L (1979) Drug metabolism in liver disease: activity of hepatic microsomal metabolizing enzymes. Clin Pharmacol Ther 26:483–492
122. Sotaniemi EA, Pelkonen RO, Puukka M (1980) Measurement of hepatic drug-metabolizing enzyme activity in man. Eur J Clin Pharmacol 17:267–274
123. Guengerich FP, Turvy CG (1991) Comparison of levels of several human microsomal cytochrome P-450 enzymes and epoxide hydrolase in normal and disease states using immunochemical analysis of surgical liver samples. J Pharmacol Exp Ther 256:1189–1194
124. Shigesawa T, Sato C, Marumo F (1992) Significance of plasma glutathione determination in patients with alcoholic and non-alcoholic liver disease. J Gastroenterol Hepatol 7:7–11
125. Barbaro G, Di Lorenzo G, Soldini M, Parrotto S, Bellomo G, Belloni G et al (1996) Hepatic glutathione deficiency in chronic hepatitis C: quantitative evaluation in patients who are HIV positive and HIV negative and correlations with plasmatic and lymphocytic concentrations and with the activity of the liver disease. Am J Gastroenterol 91:2569–2573
126. Poulsen HE, Ranek L, Andreasen PB (1981) The hepatic glutathione content in liver diseases. Scand J Clin Lab Invest 41:573–576
127. Siegers C-P, Bossen KH, Younes M, Mahlke R, Oltmanns D (1982) Glutathione and glutathione-S-transferases in the normal and diseased human liver. Pharmacol Res Commun 14:61–72
128. Prescott L, Roscoe P, Wright N, Brown S (1971) Plasma-paracetamol half-life and hepatic necrosis in patients with paracetamol overdosage. Lancet 297:519–522
129. Prescott LF, Wright N (1973) The effects of hepatic and renal damage on paracetamol metabolism and excretion following overdosage.: a pharmacokinetic study. Br J Pharmacol 49:602–613
130. Jorup-Rönström C, Beermann B, Wåhlin-Boll E, Melander A, Britton S (1986) Reduction of paracetamol and aspirin metabolism during viral hepatitis. Clin Pharmacokinet 11:250–256
131. Forrest JAH, Adriaenssens P, Finlayson NDC, Prescott LF (1979) Paracetamol metabolism in chronic liver disease. Eur J Clin Pharmacol 15:427–431
132. Forrest JA, Finlayson ND, Adjepon-Yamoah KK, Prescott LF (1977) Antipyrine, paracetamol, and lignocaine elimination in chronic liver disease. Br Med J 1:1384–1387
133. Arnman R, Olsson R (1978) Elimination of paracetamol in chronic liver disease. Acta Hepatogastroenterol (Stuttg) 25:283–286
134. Benson GD (1983) Acetaminophen in chronic liver disease. Clin Pharmacol Ther 33:95–101
135. Andreasen PB, Hutters L (1979) Paracetamol (acetaminophen) clearance in patients with cirrhosis of the liver. Acta Med Scand Suppl 624:99–105
136. Sylvie D, Thierry C, Delphine C, Pierre GM, Daniel C, Isabelle O et al (2000) Lack of toxicity of acetaminophen in patients with chronic hepatitis C: a randomized controlled trial. Gastroenterology 118:A947
137. Federal Register (2009) Rules and regulations