Pharmacokinetics and metabolism of paracetamol (Acetaminophen)

Aspirin and Related Drugs

Volumn , Issue , 2016, Pages 181-213

  Graham, G G ^a   Hicks, M ^b  

^a UNIVERSITY OF NEW SOUTH WALES   (Australia)

^b ST VINCENT S HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85051944780     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (253)

1. Abernethy, D.R., Divoll, M., Ochs, H.R., Ameer, B. and Greenblatt, D.J. 1982, Increased metabolic clearance of acetaminophen with oral contraceptives use. Obstetrics and Gynecology, 60: 338-341.
2. Abernethy, D.R., Greenblatt, D.J., Ameer, B. and Shader, R.I. 1985, Probenecid impairment of acetaminophen and lorazepam clearance: direct inhibition of ether glucuronide formation. Journal of Pharmacology and Experimental Therapeutics, 234: 345-349.
3. Aguilar, M.I., Hart, S.J. and Calder, I.C. 1988, Complete separation of urinary metabolites of paracetamol and substituted paracetamols by reversed-phase ion-pair high-performance liquid chromatography. Journal of Chromatography, 426: 315-333.
4. Al-Obaidy, S.S., McKiernan, P.J., Po, A.L.W., Glasgow, J.F.T. and Collier, P.S. 1996, Metabolism of paracetamol in children with chronic liver disease. European Journal of Clinical Pharmacology, 50: 69-76.
5. Al-Obaidy, S.S., Po, A.L.W., McKiernan, P.J., Glasgow, J.F. and Millership, J. 1995, Assay of paracetamol and its metabolites in urine, plasma and saliva of children with chronic liver disease. Journal of Pharmaceutical and Biomedical Analysis, 13: 1033-1039.
6. Amouyal, G., Larrey, D., Letteron, P., Geneve, J., Labbe, G., Belghiti, J. and Pessayre, D. 1987, Effects of methoxsalen on the metabolism of acetaminophen in humans. Biochemical Pharmacology, 36: 2349-2352.
7. Anderson, B.J. and Holford, N.H. 1997, Rectal paracetamol dosing regimens: determination by computer simulation. Paediatric Anaesthesia, 7: 451-455.
8. Anderson, B.J., Holford, N.H., Woollard, G.A. and Chan, P.L.S. 1998, Paracetamol plasma and cerebrospinal fluid pharmacokinetics in children. British Journal of Clinical Pharmacology, 46: 237-243.
9. Anderson, B.J., Holford, N.H., Woollard, G.A., Kanagasundaram, S. and Mahadevan, M. 1999, Perioperative pharmacodynamics of acetaminophen analgesia in children. Anesthesiology, 90: 411-421.
10. Anderson, B.J., Woollard, G.A. and Holford, N.H. 1995, Pharmacokinetics of rectal paracetamol after major surgery in children. Paediatric Anaesthesia, 5: 237-242.
11. Andreasen, P.B. and Hutters, L. 1979, Paracetamol (acetaminophen) clearance in patients with cirrhosis of the liver. Acta Medica Scandinavica Supplement, 624: 99-105.
12. Antlitz, A.M., Mead, J.A. and Tolentino, M.A. 1968, Potentiation of oral anticoagulant therapy by acetaminophen. Current Therapeutic Research, 10: 501-507.
13. Anundi, N., Lahteenmaki, T., Rungren, M., Moldeus, P. and Lindros, K.O. 1993, Zonation of acetaminophen metabolism and cytochrome P450 2E1-mediated toxicity studied in isolated periportal and perivenous hepatocytes. Biochemical Pharmacology, 45: 1251-1259.
14. Autret, E., Dutertre, J.P., Breteau, M., Jonville, A.P., Furet, Y. and Laugier, J. 1993, Pharmacokinetics of paracetamol in the neonate and infant after administration of propacetamol chlorohydrate. Developmental Pharmacology and Therapeutics, 20: 129-134.
15. Axworthy, D.B., Hoffmann, K.-J., Streeter, A.J., Calleman, C.J. Pascoe, G.A. and Baillie, T.A. 1988, Covalent binding of acetaminophen to mouse hemoglobin. Identification of major and minor adducts formed in vivo and implications for the nature of the arylating metabolites. Chemico-Biological Interactions, 68: 99-116.
16. Banda, P.W. and Quart, B.D. 1982, The effect of mild alcohol consumption on the metabolism of acetaminophen in man. Research Communications in Chemical Pathology and Pharmacology, 38: 57-70.
17. Banda, P.W. and Quart, B.D. 1984, The effect of alcohol on the toxicity of acetaminophen in mice. Research Communications in Chemical Pathology and Pharmacology, 43: 127-138.
18. Bannwarth, B., Netter, P., Lapicque, F., Gillet, P., Pere, P., Boccard, E., Royer, R.J. and Gaucher, A. 1992, Plasma and cerebrospinal fluid concentrations of paracetamol after a single intravenous dose of propacetamol. British Journal of Clinical Pharmacology, 34: 79-81.
19. Baraka, O.Z., Truman, C.A., Ford, J.M. and Roberts, C.J.C. 1990, The effect of propranolol on paracetamol metabolism in man. British Journal of Clinical Pharmacology, 29: 261-264.
20. Baudouin, S.V., Howdle, P., O'Grady, J.G. and Webster, N.R. 1995, Acute lung injury in fulminant hepatic failure following paracetamol poisoning. Thorax, 50: 399-402.
21. Beaulac-Baillargeon, L. and Rocheleau, S. 1994, Paracetamol pharmacokinetics during the first trimester of human pregnancy. European Journal of Clinical Pharmacology, 46: 451-454.
22. Benet, L.Z., Øie, S. and Schwartz, J.B. 1996, Design and optimization of dosage regimens; pharmacokinetic data. In: J.G. Hardman, L.E. Limbird, P.B. Molinoff and R.W. Ruddon (eds), Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th edn, p. 1712. New York: Pergamon Press.
23. Bhargava, V.O. and Hirate, J. 1989, Gastrointestinal, liver, and lung extraction ratio of acetaminophen in the rat after high dose administration. Biopharmaceutics and Drug Disposition, 10: 389-396.
24. Bitzen, P.O., Gustafsson, B., Jostell, K.G., Melander, A. and Wahlin-Boll, E. 1981, Excretion of paracetamol in human breast milk. European Journal of Clinical Pharmacology, 20: 123-125.
25. Blackledge, H.M., O'Farrell, J., Minton, N.A. and McLean, A.E. 1991, The effect of therapeutic doses of paracetamol on sulphur metabolism in man. Human and Experimental Toxicology, 10: 159-165.
26. Bock, K.W., Forster, A., Gschaidmeier, H., Brück, M., Münzel, P., Schareck, W., Fournel-Gigleux, S. and Burchell, B. 1993, Paracetamol glucuronidation by recombinant rat and human phenol UDPglucuronosyltransferases. Biochemical Pharmacology, 45: 1809-1814.
27. Bock, K.W., Schrenk, D., Forster, A., Griese, E.U., Morike, K., Brockmeier, D. and Eichelbaum, M. 1994, The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDPG glucuronyltransferases in man using sparteine, caffeine, and paracetamol as probes. Pharmacogenetics, 4: 209-218.
28. Bock, K.W., Wiltfang, J., Blume, R., Ullrich, D. and Bircher, J. 1987, Paracetamol as a test drug to determine glucuronide formation in man. Effects of inducers and of smoking. European Journal of Clinical Pharmacology, 31: 677-683.
29. Bonkovsky, H.L., Kane, R.E., Jones, D.P., Galinsky, R.E. and Banner, B. 1994, Acute hepatic and renal toxicity from low doses of acetaminophen in the absence of alcohol abuse or malnutrition: evidence for increased susceptibility to drug toxicity due to cardiopulmonary and renal insufficiency. Hepatology, 19: 1141-1148.
30. Bradley, H., Waring, R.H., Emery, P. and Arthur, V. 1991, Metabolism of low-dose paracetamol in patients with rheumatoid arthritis. Xenobiotica, 21: 689-693.
31. Bray, G.P., Harrison, P.M., O'Grady, J.G., Tredger, J.M. and Williams, R. 1992, Long-term anticonvulsant therapy worsens outcome in paracetamol-induced fulminant hepatic failure. Human and Experimental Toxicology, 11: 265-270.
32. Brodie, B.B. and Axelrod, J. 1949, The fate of acetophenetidin (phenacetin) in man and methods for the estimation of acetophenetidin and its metabolites in biological material. Journal of Pharmacology and Experimental Therapeutics, 97: 58-67.
33. Brodie, M.J., Boobis, A.R., Hampden, C., McPherson, G.A., Benjamin, I.S. and Blumgart, L.H. 1981, Antipyrine and paracetamol metabolism in obstructive jaundice. British Journal of Clinical Pharmacology, 13: 277P-278P.
34. Brown, R.D., Wilson, J.T., Kearns, G.L., Eichler, V.F., Johnson, V.A. and Bertrand, K.M. 1992, Single-dose pharmacokinetics of ibuprofen and acetaminophen in febrile children. Journal of Clinical Pharmacology, 32: 231-241.
35. Brune, K., Rainsford, K.D. and Schweitzer, A. 1980, Biodistribution of mild analgesics. British Journal of Clinical Pharmacology, 10: 279S-284S.
36. Burger, D.M., Meenhorst, P.L., Underberg, W.J., van der Heijde, J.F., Koks, C.H. and Beijnen, J.H. 1994, Short-term, combined use of paracetamol and zidovudine does not alter the pharmacokinetics of either drug. Netherlands Journal of Medicine, 44: 161-165.
37. Burkhart, K.K., Janco, N., Kulig, K.W., Rumack, B.H. 1995, Cimetidine as adjunctive treatment for acetaminophen overdose. Human and Experimental Toxicology, 14: 299-304.
38. Chamberlain, J.M., Gorman, R.L., Oderda, G.M., Klein-Schwartz, W. and Klein, B.L. 1993, Use of activated charcoal in a simulated poisoning with acetaminophen: a new loading dose for N-acetylcysteine? Annals of Emergency Medicine, 22: 1398-1402.
39. Chen, L., Mohr, S.N. and Yang, C.S. 1996, Decrease of plasma and urinary oxidative metabolites of acetaminophen after consumption of watercress by human volunteers. Clinical Pharmacology and Therapeutics, 60: 651-660.
40. Chen, T.S., Ritchie, J.P. and Lang, C.A. 1990, Life span profiles of glutathione and acetaminophen detoxification. Drug Metabolism and Disposition, 18: 882-887.
41. Chen, W., Koenigs, L.L., Thompson, S.J., Peter, R.M., Rettie, A.E., Trager, W.F. and Nelson, S.D. 1998, Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chemical Research in Toxicology, 11: 295-301.
42. Chien, J.Y., Peter, R.M., Nolan, C.M., Wartell, C., Slattery, J.T., Nelson, S.D., Carithers, R.L. and Thummel, K.E. 1997, Influence of polymorphic N-acetyltransferase phenotype on the inhibition and induction of acetaminophen bioactivation with long-term isoniazid. Clinical Pharmacology and Therapeutics, 61: 24-34.
43. Chyka, P.A., Holley, J.E., Mandrell, T.D. and Sugathan, P. 1995, Correlation of drug pharmacokinetics and effectiveness of multiple-dose activated charcoal therapy. Annals of Emergency Medicine, 25: 356-362.
44. Clements, J.A., Critchley, J.A.J.H. and Prescott, L.F. 1984, The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man. British Journal of Clinical Pharmacology, 18: 481-485.
45. Cociglio, M., Bres, J., Sauvaire, D., Alric, R. and Richard, M. 1991, Pharmacokinetics of an indomethacin pro-drug: apyramide after intravenous administration in dog. European Journal of Drug Metabolism and Pharmacokinetics, 16: 275-280.
46. Cooper, S.A., Schachtel, B.P., Goldman, E., Gelb, S. and Cohn, P. 1989, Ibuprofen and acetaminophen in the relief of acute pain: a randomized, double-blind, placebo-controlled study. Journal of Clinical Pharmacology, 29: 1026-1030.
47. Corbett, M.D., Corbett, B.R., Hannothiaux, M.-H. and Quintana, S.J. 1989, Metabolic activation and nucleic acid binding of acetaminophen and related arylamine substrates by the respiratory burst of human granulocytes. Chemical Research in Toxicology, 2: 260-266.
48. Court, M.H. and Greenblatt, D.J. 1997, Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes. Biochemical Pharmacology, 53: 1041-1047.
49. Craig, P.N. 1990, Drug compendium. In: C. Hansch, P.G. Sammes and J.B. Taylor (eds), Comprehensive Medicinal Chemistry, p. 245. Oxford: Pergamon.
50. Crippin, J.S. 1993, Acetaminophen hepatotoxicity: potentiation by isoniazid. American Journal of Gastroenterology, 88: 590-592.
51. Critchley, J.A.J.H., Dyson, E.H., Scott, A.W., Jarvie, D.R. and Prescott, L.F. 1983, Is there a place for cimetidine or ethanol in the treatment of paracetamol poisoning? Lancet, 1: 1375-1376.
52. Critchley, J.A.J.H., Nimmo, G.R., Gregson, C.A., Woolhouse, N.M. and Prescott, L.F. 1986, Intersubject and ethnic differences in paracetamol metabolism. British Journal of Clinical Pharmacology, 22: 649-657.
53. Cummings, A.J., King, M.L. and Martin, B.K. 1967, A kinetic study of drug elimination: the excretion of paracetamol and its metabolites in man. British Journal of Pharmacology and Chemotherapy, 29: 150-157.
54. Dawson, J., Knowles, R.G. and Pogson, C.I. 1991, Quantitative studies of sulphate conjugation by isolated rat liver cells using [35S]sulphate. Biochemical Pharmacology, 42: 45-49.
55. Dawson, J., Knowles, R.G. and Pogson, C.I. 1992, Measurement of glucuronidation by isolated rat liver cells using [14C] fructose. Biochemical Pharmacology, 43: 971-978.
56. de Morais, S.M.F., Uetrecht, J.P. and Wells, P.G. 1992a, Decreased glucuronidation and increased bioactivation of acetaminophen in Gibert's syndrome. Gastroenterology, 102: 577-586.
57. de Morais, S.M.F., Uetrecht, J.P. and Wells, P.G. 1992b, Biotransformation and toxicity of acetaminophen in congenic RHA rats with or without a hereditary deficiency in bilirubin UDP-glucuronsyltransferase. Toxicology and Applied Pharmacology, 117: 81-87.
58. de Wildt, S.N., Kearns, G.L., Leeder, J.S. and van den Anker, J.N. 1999, Glucuronidation in humans. Pharmacogenetic and development aspects. Clinical Pharmacokinetics, 36: 439-452.
59. Divoll, M., Abernethy, D.R., Ameer, B. and Greenblatt, D.J. 1982, Acetaminophen kinetics in the elderly. Clinical Pharmacology and Therapeutics, 31: 151-156.
60. Dolara, P., Lodovici, M., Salvadori, M., Saltutti, C., Delle Rose, A., Selli, C. and Kriebel, D. 1988, Variations of cortisol hydroxylation and paracetamol metabolism in patients with bladder carcinoma. British Journal of Urology, 62: 419-426.
61. Duggin, G.G. and Mudge, G.H. 1975, Renal tubular transport of paracetamol and its conjugates in the dog. British Journal of Pharmacology, 54: 359-366.
62. Dybing, E., Holme, J.A., Gordon, W.P., Soderlund, E.J., Dahlin, D.C. and Nelson, S.D. 1984, Genotoxicity studies with paracetamol. Mutation Research, 138: 21-32.
63. Epstein, M.M., Nelson, S.D., Slattery, J.T., Kalhorn, T.F., Wall, R.A. and Wright, J.M. 1991, Inhibition of the metabolism of paracetamol by isoniazid. British Journal of Clinical Pharmacology, 31: 139-142.
64. Esteban, A. and Perez-Mateo, M. 1999, Heterogeneity of paracetamol metabolism in Gilbert's syndrome. European Journal of Drug Metabolism and Pharmacokinetics, 24: 9-13.
65. Esteban, A., Perez-Mateo, M., Boix, V., Gonzalez, M., Portilla, J. and Mora, A. 1997, Abnormalities in the metabolism of acetaminophen in patients infected with the human immunodeficiency virus (HIV). Methods and Findings in Experimental and Clinical Pharmacology, 19: 129-132.
66. Eyanagi, R., Hisanari, Y. and Shigematsu, H. 1991, Studies of paracetamol/phenacetin toxicity: isolation and characterization of p-aminophenol-glutathione conjugate. Xenobiotica, 21: 793-803.
67. Fischer, V., West, P.R., Harman, L.S. and Mason, R.P. 1985, Free radical metabolites of acetaminophen and a dimethylated derivative. Environmental Health Perspectives, 64: 127-137.
68. Flinn, F.B. and Brodie, B.B. 1948, The effect on the pain threshold of N-acetyl-p-aminophenol, a product derived in the body from acetanilide. Journal of Pharmacology and Experimental Therapeutics, 94: 76-77.
69. Forrest, J.A., Adriaenssens, P., Finlayson, N.D. and Prescott, L.F. 1979, Paracetamol metabolism in chronic liver disease. European Journal of Clinical Pharmacology, 15: 427-431.
70. Fort, D.J., Rayburn, J.R. and Bantle, J.A. 1992, Evaluation of acetaminophen-induced developmental toxicity using FETAX. Drug and Chemical Toxicology, 15: 329-350.
71. Froomes, P.R., Morgan, D.J., Smallwood, R.A. and Angus, P.W. 1999, Comparative effects of oxygen supplementation on theophylline and acetaminophen clearance in human cirrhosis. Gastroenterology, 117: 1257-1259.
72. Gaudreault, P., Guay, J., Nicol, O. and Dupuis, C. 1988, Pharmacokinetics and clinical efficacy of intrarectal solution of acetaminophen. Canadian Journal of Anaesthesia, 35: 149-152.
73. Gawronska-Szklarz, B., Gabriel, J. and Wojcicki, J. 1988, Pharmacokinetics of paracetamol in patients with stomach cancer. Polish Journal of Pharmacology and Pharmacy, 40: 41-45.
74. Gemborys, M.W. and Mudge, G.H. 1981, Formation and disposition of the minor metabolites of acetaminophen in the hamster. Drug Metabolism and Disposition, 9: 340-351.
75. Genter, M.B., Liang, H.C., Gu, J., Ding, X., Negishi, M., McKinnon, R.A. and Nebert, D.W. 1998, Role of CYP2A5 and 2G1 in acetaminophen metabolism and toxicity in the olfactory mucosa of the CYP1a2(α/α) mouse. Biochemical Pharmacology, 55: 1819-1826.
76. Gentry, C.A., Paloucek, F.P. and Rodvold, K.A. 1994, Prediction of acetaminophen concentrations in overdose patients using a Bayesian pharmacokinetic model. Journal of Toxicology - Clinical Toxicology, 32: 17-30.
77. Girre, C., Hispard, E., Palombo, S., N'Guyen, C. and Dally, S. 1994, Increased metabolism of acetaminophen in chronically alcoholic patients. Alcoholism, Clinical and Experimental Research, 17: 170-173.
78. Glynn, J.P. and Bastain, W. 1973, Salivary excretion of paracetamol in man. Journal of Pharmacy and Pharmacology, 25: 420-421.
79. Graham, G.G., Milligan, M.K., Day, R.O., Williams, K.M. and Ziegler, J.B. 1997, Therapeutic considerations from pharmacokinetics and metabolism: ibuprofen and paracetamol. In: K.D. Rainsford and M.C. Powanda (eds), Safety and Efficacy of Non-prescription (Over-the-Counter) Analgesics and NSAIDs. pp. 72-92. Dordrecht: Kluwer Press.
80. Graham, G.G., Day, R.O., Milligan, M.K., Ziegler, J.B. and Kettle, A.J. 1999, Current concepts of the actions of paracetamol (acetaminophen) and NSAIDs. Inflammopharmacology, 7: 255-263.
81. Gramatte, T. and Richter, K. 1994, Paracetamol absorption from different sites in the human small intestine. British Journal of Clinical Pharmacology, 37: 608-611.
82. Gregus, Z., Madhu, C. and Klaassen, C.D. 1988, Species variation in toxication and detoxication of acetaminophen in vivo: a comparative study of biliary and urinary excretion of acetaminophen metabolites. Journal of Pharmacology and Experimental Therapeutics, 244: 91-99.
83. Gregus, Z., Oguro, T. and Klaassen, C.D. 1994, Nutritionally and chemically induced impairment of sulfate activation and sulfation of xenobiotics in vivo. Chemico-Biological Interactions, 92: 169-177.
84. Griener, J.C., Msall, M.E., Cooke, R.E. and Corcoran, G.B. 1990, Noninvasive determination of acetaminophen disposition in Down's syndrome. Clinical Pharmacology and Therapeutics, 48: 520-528.
85. Haderslev, K.V., Sonne, J., Poulsen, H.E. and Loft, S. 1998, Paracetamol metabolism in patients with ulcerative colitis. British Journal of Clinical Pharmacology, 46: 513-516.
86. Hammond, P.M., Scawen, M.D. and Price, C.P. 1981, Enzyme-based paracetamol estimation. Lancet, 1: 391-392.
87. Hart, S.G., Beierschmitt, W.P., Wyand, D., Khairallah, E.A. and Cohen, S.D. 1994, Acetaminophen nephrotoxicity in CD-1 mice. I. Evidence of a role for in situ activation in selective covalent binding and toxicity. Toxicology and Applied Pharmacology, 126: 267-275.
88. Hassig, S.R., Linscheer, W.G., Murthy, U.K., Miller, C., Banerjee, A., Levine, L., Wagner, K. and Oates, R.P. 1993, Effects of PEG-electrolyte (Colyte) lavage on serum acetaminophen concentrations. A model for treatment of acetaminophen overdose. Digestive Diseases and Sciences, 38: 1395-1401.
89. Heading, R.C., Nimmo, J., Prescott, L.F. and Tothill, P. 1973, The dependence of paracetamol absorption on the rate of gastric emptying. British Journal of Pharmacology, 47: 415-421.
90. Henderson, C.J., Wolf, C.R., Kitteringham, N., Powell, H. and Park, B.K. 2000, Increased resistance to acetaminophen hepatotoxicity in mice lacking glutathione S-transferase. Proceedings of the National Academy of Sciences USA, 97: 12741-12745.
91. Hepler, B., Weber, J., Sutheimer, C. and Sunshine, I. 1984, Homogenous enzyme immunoassay of acetaminophen in serum. American Journal of Clinical Pathology, 81: 602-610.
92. Herd, B., Wynne, H., Wright, P., James, O. and Woodhouse, K. 1991, The effect of age on glucuronidation and sulphation of paracetamol by human liver fractions. British Journal of Clinical Pharmacology, 32: 768-770.
93. Hindmarsh, K.W., Mayers, D.J., Wallace, S.M., Danilkewich, A. and Ernst, A. 1991, Increased serum sulfate concentrations in man due to environmental factors: effects on acetaminophen metabolism. Veterinary and Human Toxicology, 33: 441-445.
94. Hinson, J.A., Pohl, L.R., Monks, T.J. and Gillette, J.R. 1981, Acetaminophen-induced hepatotoxicity. Life Sciences, 29: 107-116.
95. Hinson, J.A., Roberts, D.W., Benson, R.W., Dalhoff, K., Loft, S. and Poulsen, H.E. 1990, Mechanism of paracetamol toxicity. Lancet, 1: 732.
96. Hoffman, D.A., Wallace, S.M. and Verbeeck, R.K. 1990, Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics. European Journal of Clinical Pharmacology, 39: 143-148.
97. Hoffmann, K.J., Axworthy, D.B. and Baillie, T.A. 1990, Mechanistic studies on the metabolic activation of acetaminophen in vivo. Chemical Research in Toxicology, 3: 204-211.
98. Hoivik, D.J., Manautou, J.E., Tveit, A., Hart, S.G., Khairallah, E.A. and Cohen, S.D. 1995, Genderrelated differences in susceptibility to acetaminophen-induced protein arylation and nephrotoxicity in the CD-1 mouse. Toxicology and Applied Pharmacology, 130: 257-271.
99. Hongslo, J.K., Smith, C.V., Brunborg, G., Soderlund, E.J. and Holme, J.A. 1994, Genotoxicity of paracetamol in mice and rats. Mutagenesis, 9: 93-100.
100. Hutabarat, R.M., Unadkat, J.D., Kushmerick, P., Aitken, M.L., Slattery, J.T. and Smith, A.L. 1991, Disposition of drugs in cystic fibrosis. III. Acetaminophen. Clinical Pharmacology and Therapeutics, 50: 695-701.
101. Inaba, T., Mahon, W.A. and Stone, R.M. 1979, Phenacetin concentrations in portal and hepatic venous blood in man. International Journal of Clinical Pharmacology and Biopharmacy, 17: 371-374.
102. Iqbal, N., Ahmad, B., Janbaz, K.H., Gilani, A.U. and Niazi, S.K. 1995, The effect of caffeine on the pharmacokinetics of acetaminophen in man. Biopharmaceutics and Drug Disposition, 16: 481-487.
103. Jayasinghe, K.S.A., Roberts, C.J.C. and Read, A.E. 1986, Is biliary excretion of paracetamol significant in man?' British Journal of Clinical Pharmacology, 22: 363-366.
104. Jeffery, E.H., Arndt, K. and Haschek, W.M. 1988, Mechanism of inhibition of hepatic bioactivation of paracetamol by dimethyl sulfoxide. Drug Metabolism and Drug Interactions, 6: 413-424.
105. Jollow, D.J., Thorgeirsson, S.S., Potter, W.Z., Hashimoto, M. and Mitchell, J.R. 1974, Acetaminophen- induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen. Pharmacology, 12: 251-271.
106. Kahn, G.C., Boobis, A.R. and Brodie, M.J. 1985, Phenacetin O-de-ethylase: an activity of a cytochrome P450 showing genetic linkage with that catalysing the 4-hydroxylation. British Journal of Clinical Pharmacology, 20: 67-76.
107. Kalabis, G.M. and Wells, P.G. 1990, Biphasic modulation of acetaminophen bioactivation and hepatotoxicity by pretreatment with the interferon inducer polyinosinic-polycytidylic acid. Journal of Pharmacology and Experimental Therapeutics, 255: 1408-1419.
108. Kamali, F. 1993, The effect of probenecid on paracetamol metabolism and pharmacokinetics. European Journal of Clinical Pharmacology, 45: 551-553.
109. Kamali, F., Edwards, C. and Rawlins, M.D. 1992, The effect of pirenzipine on gastric emptying and salivary flow rate: constraints on the use of saliva paracetamol concentrations for the determination of paracetamol pharmacokinetics. British Journal of Clinical Pharmacology, 33: 309-312.
110. Kelley, M.T., Walson, P.D., Edge, J.H., Cox, S. and Mortensen, M.E. 1992, Pharmacokinetics and pharmacodynamics of ibuprofen isomers and acetaminophen in febrile children. Clinical Pharmacology and Therapeutics, 52: 181-189.
111. Kietzmann, D., Bock, K.W., Krahmer, B., Kettler, D. and Bircher, J. 1990, Paracetamol test: modification by renal function, urine flow and pH. European Journal of Clinical Pharmacology, 39: 245-251.
112. Kim, H.J., Rozman, P., Madhu, C. and Klaassen, C.D. 1992, Homeostasis of sulphate and 3- phosphoadenosine 5-phosphosulfate in rats after acetaminophen administration. Journal of Pharmacology and Experimental Therapeutics, 261: 1015-1021.
113. Kirkland, D.J., Dresp, J.H., Marshall, R.R., Baumeister, M., Gerloff, C. and Gocke, E. 1992, Normal chromosomal aberration frequencies in peripheral lymphocytes of healthy human volunteers exposed to a maximum daily dose of paracetamol in a double blind trial. Mutation Research, 279: 181-194.
114. Kociscova, J., Rossner, P., Binkova, B., Bavorova, H. and Sram, R.J. 1988, Mutagenicity studies on paracetamol in human volunteers: I. Cytogenetic analysis of peripheral lymphocytes and lipid peroxidation in plasma. Mutation Research, 209: 161-165.
115. Koymans, L., Donné-op den Kelder, G.M., te Koppele, J.M. and Vermeulen, N.P.E. 1993, Generalized cytochrome P450-mediated oxidation and oxygenation reactions in aromatic substrates with activated N-H, O-H, or S-H substituents. Xenobiotica, 23: 633-648.
116. Kuntzman, R., Pantuck, E.J., Kaplan, S.A. and Conney, A.H. 1977, Phenacetin metabolism: effect of hydrocarbons and cigarette smoking. Clinical Pharmacology and Therapeutics, 22: 757-764.
117. Landin, J.S., Cohen, S.D. and Khairallah, E.A. 1996, Identification of a 54-kDa mitochondrial acetaminophen- binding protein as aldehyde dehydrogenase. Toxicology and Applied Pharmacology, 141: 299-307.
118. Lau, G.S. and Critchley, J.A.J.H. 1994, The estimation of paracetamol and its major metabolites in both plasma and urine by a single high-performance liquid chromatographic assay. Journal of Pharmaceutical and Biomedical Analysis, 12: 1563-1572.
119. Lauterburg, B.H. 2002, Analgesics and glutathione. American Journal of Therapeutics, 9: 225-233.
120. Lee, C.A., Thummel, K.E., Kalhorn, T.F., Nelson, S.D. and Slattery, J.T. 1991, Activation of acetaminophen-reactive formation by methylxanthines and known cytochrome P450 activators. Drug Metabolism and Disposition, 19: 966-971.
121. Lee, H.S., Ti, T.Y., Koh, Y.K. and Prescott, L.F. 1992, Paracetamol elimination in Chinese and Indians in Singapore. European Journal of Clinical Pharmacology, 43: 81-84.
122. Lee, H.S., Ti, T.Y., Lye, W.C., Khoo, Y.M. and Tan, C.C. 1996, Paracetamol and its metabolites in saliva and plasma in chronic dialysis patients. British Journal of Clinical Pharmacology, 41: 41-47.
123. Lester, D. and Greenberg, L.A. 1947, The metabolic fate of acetanilid and other aniline derivatives: II. Major metabolites of acetanilid appearing in the blood. Journal of Pharmacology and Experimental Therapeutics, 90: 68-75.
124. Leung, N.W.Y. and Critchley, J.A.J.H. 1991, Increased oxidative metabolism of paracetamol in patients with hepatocellular carcinoma. Cancer Letters, 57: 45-48.
125. Levy, G. 1987, Pharmacokinetic analysis of the analgesic effect of a second dose of acetaminophen in humans. Journal of Pharmaceutical Sciences, 76: 88-89.
126. Levy, G., Khanna, N.N., Soda, D.M., Tzuzuki, O. and Stern, L. 1975, Pharmacokinetics of acetaminophen in the human neonate: formation of acetaminophen glucuronide and sulfate in relation to plasma bilirubin concentration and D-glucaric acid excretion. Pediatrics, 55: 818-825.
127. Lewis, R.P., Dunphy, J.A. and Reilly, C.S. 1991, Paracetamol metabolism after general anaesthesia. European Journal of Anaesthesiology, 8: 445-450.
128. Li, Y., Wang, E., Patten, C.J., Chen, L. and Yang, C.S. 1994, Effects of flavonoids on cytochrome P450-dependent acetaminophen metabolism in rats and human liver microsomes. Drug Metabolism and Disposition, 22: 566-571.
129. Liu, J., Liu, Y., Madhu, C. and Klaasen, C.D. 1993, Protective effects of oleanolic acid on acetaminophen-induced hepatotoxicity in mice. Journal of Pharmacology and Experimental Therapeutics, 266: 1607-1613.
130. Liu, J., Sato, C. and Marumo, F. 1991, Characterization of the acetaminophen-glutathione conjugation reaction by liver microsomes: species difference in the effects of acetone. Toxicology Letters, 56: 269-274.
131. Manyike, P.T., Kharasch, E.D., Kalhorn, T.F. and Slattery, J.T. 2000, Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation. Clinical Pharmacology and Therapeutics, 67: 275-282.
132. Martin, U., Temple, R.M., Winney, R.J. and Prescott, L.F. 1993, The disposition of paracetamol and its conjugates during multiple dosing in patients with end-stage renal failure maintained on haemodialysis. European Journal of Clinical Pharmacology, 45: 141-145.
133. Marzo, A., Quadro, G., Treffner, E., Ripamonti, M., Meroni, G. and Lucarelli, C. 1990, Highpressure liquid chromatographic evaluation of cyclic paracetamol-acetylsalicylate and its active metabolites with results of a comparative pharmacokinetic investigation in the rat. Arzneimittel- Forschung, 40: 813-817.
134. Mason, R.P. and Fischer, V. 1986, Free radicals of acetaminophen: their subsequent reactions and toxicological significance. Federation Proceedings, 45: 2493-2499.
135. Mason, R.P. and Fisher, V. 1992, Possible role of free radical formation in drug-induced agranulocytosis. Drug Safety, 7 (Suppl. 1): 45-50.
136. McPhail, M.E., Knowles, R.G., Salter, M., Dawson, J., Burchell, B. and Pogson, C.I. 1993, Uptake of acetaminophen (paracetamol) by isolated rat liver cells. Biochemical Pharmacology, 45: 1599-1604.
137. Miller, R.P., Roberts, R.J. and Fischer, L.J. 1976, Acetaminophen elimination kinetics in neonates, children and adults. Clinical Pharmacology and Therapeutics, 19: 284-294.
138. Miners, J.O., Attwood, J. and Birkett, D.J. 1983, Influence of sex and oral contraceptive steroids on paracetamol metabolism. British Journal of Clinical Pharmacology, 16: 503-509.
139. Miners, J.O., Attwood, J. and Birkett, D.J. 1984, Determinants of acetaminophen metabolism: effect of inducers and inhibitors of drug metabolism on acetaminophen's metabolic pathways. Clinical Pharmacology and Therapeutics, 35: 480-486.
140. Miners, J.O., Osborne, N.J., Tonkin, A.L. and Birkett, D.J. 1992, Perturbation of paracetamol urinary metabolic ratios by urine flow rate. British Journal of Clinical Pharmacology, 34: 359-362.
141. Miners, J.O., Penhall, R., Robson, R.A. and Birkett, D.J. 1988, Comparison of paracetamol metabolism in young adult and elderly males. European Journal of Clinical Pharmacology, 35: 157-160.
142. Miners, J.O., Robson, R.A. and Birkett, D.J. 1986, Paracetamol metabolism in pregnancy. British Journal of Clinical Pharmacology, 22: 359-362.
143. Mitchell, J.R., Jollow, D.J., Potter, W.Z., Davis, D.C., Gillette, J.R. and Brodie, B.B. 1973a, Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism. Journal of Pharmacology and Experimental Therapeutics, 187: 185-194.
144. Mitchell, J.R., Jollow, D.J., Potter, W.Z., Gillette, J.R. and Brodie, B.B. 1973b, Acetaminopheninduced hepatic necrosis. IV. Protective role of glutathione. Journal of Pharmacology and Experimental Therapeutics, 187: 211-217.
145. Mitchell, M., Hanew, T., Meredith, C.G. and Schenker, S. 1983, Effects of oral contraceptive steroids on acetaminophen metabolism and elimination. Clinical Pharmacology and Therapeutics, 34: 48-53.
146. Mitchell, M.C., Schenker, A., Avant, G.R. and Speeg, K.V. 1981, Cimetidine protects against acetaminophen hepatotoxicity in rats. Gastroenterology, 81: 1052-1060.
147. Miyauchi, T., Ishikawa, M., Tashiro, S., Hisaeda, H., Nagasawa, H. and Himeno, K. 1997, Acetaminophen absorption test as a marker of small bowel transplant rejection. Transplantation, 63: 1179-1182.
148. Moreau, X., Le Quay, L., Granry, J.C., Boishardy, N. and Delhumeau, A. 1993, Pharmacokinetics of paracetamol in the cerebrospinal fluid in the elderly. Therapie, 48: 393-396.
149. Moulding, T.S., Redeker, A.G. and Kanel, G.C. 1991, Acetaminophen, isoniazid and hepatic toxicity. Annals of Internal Medicine, 114: 431.
150. Mucklow, J.C., Fraser, H.S., Bulpitt, C.J., Kahn, C., Mould, G. and Dollery, C.T. 1980, Environmental factors affecting paracetamol metabolism in London factory and office workers. British Journal of Clinical Pharmacology, 10: 67-74.
151. Mugford, C.A. and Tarloff, J.B. 1997, The contribution of oxidation and deacetylation to acetaminophen nephrotoxicity in female Sprague-Dawley rats. Toxicology Letters, 93: 15-22.
152. Müller, M., Schmid, R., Georgopoulos, A., Buxbaum, A., Wasicek, C. and Eichler, H.G. 1995, Application of microdialysis to clinical pharmacokinetics in humans. Clinical Pharmacology and Therapeutics, 57: 371-380.
153. Murphy, L.J. and Galley, P.T. 1994, Measurement in vitro of human plasma glycerol with a hydrogen peroxide detecting microdialysis enzyme electrode. Analytical Chemistry, 66: 4345-4353.
154. Murphy, R., Swartz, R. and Watkins, P.B. 1990, Severe acetaminophen toxicity in a patient receiving isoniazid. Annals of Internal Medicine, 113: 799-800.
155. Mutlib, A.E., Shockcor, J., Espina, R., Graciani, N., Du, A. and Gan, L.S. 2000, Disposition of glutathione conjugates in rats by a novel glutamic acid pathway: characterization of unique peptide conjugates by liquid chromatography/mass spectrometry and liquid chromatography/NMR. Journal of Pharmacology and Experimental Therapeutics, 294: 735-745.
156. Myers, T.B., Thummel, K.E., Kalhorn, T.F. and Nelson, S.D. 1994, Preferred orientations in the binding of 4-hydroxyacetanilide (acetaminophen) to cytochrome P450 1A1 and 2B1 isoforms as determined by 13C- and 15N-NMR relaxation studies. Journal of Medicinal Chemistry, 37: 860-867.
157. Naga Rani, M.A., Joseph, T., Narayanan, R. 1989, Placental transfer of paracetamol. Journal of the Indian Medical Association, 87: 182-183.
158. Nakamura, J., Baba, S., Nakamura, T., Sasaki, H. and Shibasaki, J. 1987, A method for the preparation of calibration curves for acetaminophen glucuronide and acetaminophen sulfate in rabbit urine without the use of authentic compounds in high-performance liquid chromatography. Journal of Pharmacobio-Dynamics, 10: 673-677.
159. Nicholls, A.W., Caddick, S., Wilson, I.D., Farrant, R.D., Lindon, J.C. and Nicholson, J.K. 1995, High resolution NMR spectroscopic studies on the metabolism and futile deacetylation of 4-hydroxy acetanilide (paracetamol) in the rat. Biochemical Pharmacology, 49: 1155-1164.
160. Nicholls, A.W., Farrant, R.D., Shockcor, J.P., Unger, S.E., Wilson, I.D., Lindon, J.C. and Nicholson, J.K. 1997, NMR and HPLC-NMR spectroscopic studies of futile deacetylation in paracetamol metabolites in rat and man. Journal of Pharmaceutical and Biomedical Analysis, 15: 901-910.
161. Nicholson, J.K., Timbrell, J.A., Bales, J.R. and Sadler, P.J. 1985, A high resolution proton nuclear magnetic resonance approach to the study of hepatocyte and drug metabolism. Application to acetaminophen. Molecular Pharmacology, 27: 634-643.
162. Nolan, C.M., Sandblom, R.E., Thummel, K.E., Slattery, J.T. and Nelson, S.D. 1994, Hepatotoxicity associated with acetaminophen usage in patients receiving multiple drug therapy for tuberculosis. Chest, 105: 408-411.
163. Notarianni, L.J., Oldham, H.G. and Bennett, P.N. 1987, Passage of paracetamol into breast milk and its subsequent metabolism by the neonate. British Journal of Clinical Pharmacology, 24: 63-67.
164. O'Brien, P.J., Khan, S. and Jatoe, S.D. 1990, Formation of biological reactive intermediates by peroxidases: halide mediated acetaminophen oxidation and cytotoxicity. Advances in Experimental Medicine and Biology, 283: 51-64.
165. Øie, S., Lowenthal, D.T., Briggs, W.A. and Levy, G. 1975, Effect of hemodialysis on kinetics of acetaminophen by anephric patients. Clinical Pharmacology and Therapeutics, 18: 680-686.
166. Osborne, N.J., Tonkin, A.L. and Miners, J.O. 1991, Interethnic differences in drug glucuronidation: a comparison of paracetamol metabolism in Caucasians and Chinese. British Journal of Clinical Pharmacology, 32: 765-767.
167. Owen, S.G., Francis, H.W. and Roberts, M.S. 1994, Disappearance kinetics of solutes from synovial fluid after intra-articular injection. British Journal of Clinical Pharmacology, 38: 349-355.
168. Pang, K.S., Barker, F., Simard, A., Schwab, A.J. and Goresky, C.A. 1995, Sulfation of acetaminophen by the perfused rat liver: effect of red blood cell carriage. Hepatology, 22: 267-282.
169. Park, K.S., Sohn, D.H., Veech, R.L. and Song, B.J. 1993, Translational activation of ethanolinducible cytochrome P450 (CYP2E1) by isoniazid. European Journal of Pharmacology, 248: 7-14.
170. Patel, M., Tang, B. and Kalow, W. 1993, Variability of acetaminophen metabolism in Caucasians and Orientals. Pharmacogenetics, 2: 38-45.
171. Perucca, E. and Richens, A. 1979, Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs. British Journal of Clinical Pharmacology, 7: 201-206.
172. Piletta, P., Porchet, H.C. and Dayer, P. 1991, Central analgesic effect of acetaminophen but not of aspirin. Clinical Pharmacology and Therapeutics, 49: 350-354.
173. Potter, D.W. and Hinson, J.A. 1986, Mechanisms of acetaminophen oxidation to N-acetyl-P-benzoquinone by horseradish peroxidase and cytochrome P-450. Journal of Biological Chemistry, 262: 966-973.
174. Potter, D.W. and Hinson, J.A. 1987, The 1- and 2-electron oxidation of acetaminophen catalyzed by prostaglandin H synthase. Journal of Biological Chemistry, 262: 974-980.
175. Poulsen, H.E., Ranek, L. and Jorgensen, L. 1991, The influence of disulfiram on acetaminophen metabolism in man. Xenobiotica, 21: 243-249.
176. Prescott, L.F. 1980, Kinetics and metabolism of paracetamol and phenacetin. British Journal of Clinical Pharmacology, 10: 291S-298S.
177. Prescott, L.F. 2000, Paracetamol, alcohol and the liver. British Journal of Clinical Pharmacology, 49: 291-301.
178. Prescott, L.F., Critchley, J.A.J.H., Balali-Mood, M. and Pentland, B. 1981, Effects of microsomal enzyme induction on paracetamol metabolism in man. British Journal of Clinical Pharmacology, 12: 149-153.
179. Prescott, L.F., Speirs, G.C., Critchley, J.A.J.H., Temple, R.M. and Winney, R.J. 1989, Paracetamol disposition and metabolite kinetics in patients with chronic renal failure. European Journal of Clinical Pharmacology, 36: 291-297.
180. Proudfoot, A.T. 1982, Diagnosis and Treatment of Acute Poisoning. Oxford: Blackwell.
181. Quiding, H., Oikarinen, V., Sane, J. and Sjöblad, A.-M. 1984, Analgesic efficacy after single and repeated doses of codeine and acetaminophen. Journal of Clinical Pharmacology, 24: 27-34.
182. Rainska-Giezek, T. 1995, Influence of caffeine on the toxicity and pharmacokinetics of paracetamol. Annales Academiae Medicae Stetinensis, 41: 69-85.
183. Ramakrishna, B.S., Roberts-Thomson, I.C., Pannall, P.R. and Roediger, W.E. 1991, Impaired sulphation of phenol by the colonic mucosa in quiescent and active ulcerative colitis. Gut, 32: 46-49.
184. Rannug, U., Holme, J.A., Hongslo, J.K. and Sram, R. 1995, An evaluation of the genetic toxicity of paracetamol. Mutation Research, 327: 179-200.
185. Rawlins, M.D., Henderson, D.B. and Hijab, A.R. 1977, Pharmacokinetics of paracetamol (acetaminophen) after intravenous and oral administration. European Journal of Clinical Pharmacology, 11: 283-286.
186. Ray, K., Sahana, C.C., Chaudhuri, S.B., De, G.C. and Chatterjee, K. 1993, Effects of trichloroethylene anaesthesia on salivary paracetamol elimination. Indian Journal of Physiology and Pharmacology, 37: 79-81.
187. Rayburn, W., Shukla, U., Stetson, P. and Piehl, E. 1986, Acetaminophen pharmacokinetics: comparison between pregnant and nonpregnant women. American Journal of Obstetrics and Gynecology, 155: 1353-1356.
188. Renwick, A.G., Ahsan, C.H., Challenor, V.F., Daniels, R., Macklin, B.S., Waller, D.G. and George, C.F. 1992, The influence of posture on the pharmacokinetics of orally administered nifedipine. British Journal of Clinical Pharmacology, 34: 332-336.
189. Richard, A., Hongslo, J.K., Boone, P.F. and Holme, J.A. 1991, Structure-activity of paracetamol analogues: inhibition of replicative DNA synthesis in V79 Chinese hamster cells. Chemical Research in Toxicology, 4: 151-156.
190. Roberts, D.W., Bucci, T.J., Benson, R.W., Warbritton, A.R., McRae, T.A., Pumford, N.R. and Hinson, J.A. 1991, Immunohistochemical localization and quantification of the 3-(cystein-S-yl)-acetaminophen protein adduct in acetaminophen hepatotoxicity. American Journal of Pathology, 38: 359-371.
191. Roberts, J.R., Gracely, E.J. and Schoffstall, J.M. 1997, Advantage of high-surface-area charcoal for gastrointestinal decontamination in a human acetaminophen ingestion model. Academic Emergency Medicine, 4: 167-174.
192. Robertson, D.R., Higginson, I., Macklin, B.S., Renwick, A.G., Waller, D.G. and George, C.F. 1991, The influence of protein containing meals on the pharmacokinetics of levodopa in healthy volunteers. British Journal of Clinical Pharmacology, 31: 413-417.
193. Rogers, L.K., Moorthy, B. and Smith, C.V. 1997, Acetaminophen binds to mouse hepatic and renal DNA at human therapeutic doses. Chemical Research in Toxicology, 10: 470-476.
194. Rogers, S.M., Back, D.J., Stevenson, P.J., Grimmer, S.F.M. and Orme, M.L'E. 1987, Paracetamol interaction with oral contraceptive steroids: increased plasma concentrations of ethinyloestradiol. British Journal of Clinical Pharmacology, 23: 721-725.
195. Rollins, D.E., von Bahr, C., Glaumann, H., Moldeus, P. and Rane, A. 1979, Acetaminophen: potentially toxic metabolite formed by human fetal and adult liver microsomes and isolated fetal liver cells. Science, 205: 1414-1416.
196. Romanelli, L., Valeri, P., Morrone, L.A. and Pimpinella, G. 1991, Ocular disposition of acetaminophen and its metabolites following intravenous administration in rabbits. Journal of Ocular Pharmacology, 7: 339-350.
197. Rudd, G.D., Donn, K.H. and Grisham, J.W. 1981, Prevention of acetaminophen-induced hepatic necrosis by cimetidine in mice. Research Communications in Chemical Pathology and Pharmacology, 32: 369-372.
198. Rumble, R.H., Roberts, M.S. and Denton, M.J. 1991, Effects of posture and sleep on the pharmacokinetics of paracetamol (acetaminophen) and its metabolites. Clinical Pharmacokinetics, 20: 167-173.
199. Ryan, D.E., Koop, D.R., Thomas, P.E., Coon, M.J. and Levin, W. 1986, Evidence that isoniazid and ethanol induce the same microsomal P-450 in rat liver, an isozyme homologous to rabbit liver cytochrome P-450 isoenzyme 3a. Archives of Biochemistry and Biophysics, 246: 633-644.
200. Sabater, J., Domenech, J. and Obach, R. 1993, Pharmacokinetic study of 4-acetamidophenyl-2-(5- p-toluyl-1-methylpyrrole)acetate in the rat. Arzneimittel-Forschung, 43: 154-159.
201. Sahajwalla, C.G. and Ayres, J.W. 1991, Multiple-dose acetaminophen pharmacokinetics. Journal of Pharmaceutical Sciences, 80: 855-860.
202. Saincher, A., Sitar, D.S. and Tenenbein, M. 1997, Efficacy of ipecac during the first hour after drug ingestion in human volunteers. Journal of Toxicology, 35: 609-615.
203. Sakuma-Sawada, N., Iida, S., Mizuma, T., Hayashi, M. and Awazu, S. 1997, Inhibition of the hepatic uptake of paracetamol sulphate by anionic compounds. Journal of Pharmacy and Pharmacology, 49: 743-746.
204. Sato, C., Liu, J., Miyakawa, H., Nouchi, T., Tanaka, Y., Uchihara M. and Marumo, F. 1991, Inhibition of acetaminophen activation by ethanol and acetaldehyde in liver microsomes. Life Sciences, 49: 1787-1791.
205. Sato, C. and Marumo, F. 1991, Synergistic effect of NADH on NADPH-dependent acetaminophen activation in liver microsomes and its inhibition by cyanide. Life Sciences, 48: 2423-2427.
206. Savides, M.C., Oehme, F.W., Nash, S.L. and Leipold, H.W. 1984, The toxicity and biotransformation of single doses of acetaminophen in dogs and cats. Toxicology and Applied Pharmacology, 74: 26-34.
207. Scavone, J.M., Greenblatt, D.J., Blyden, G.T., Luna, B.G. and Harmatz, J.S. 1990a, Validity of a two-point acetaminophen pharmacokinetic study. Therapeutic Drug Monitoring, 12: 35-39.
208. Scavone, J.M., Greenblatt, D.J., LeDuc, B.W., Blyden, G.T., Luna, B.G. and Harmatz, J.S. 1990b, Differential effect of cigarette smoking on antipyrine oxidation versus acetaminophen conjugation. Pharmacology, 40: 77-84.
209. Scott, D.O., Sorenson, L.R., Steele, K.L., Puckett, D.L. and Lunte, C.E. 1991, In vivo microdialysis sampling for pharmacokinetic investigations. Pharmaceutical Research, 8: 389-392.
210. Sesardic, D., Boobis, A.R., Edwards, R.J. and Davies, D.S. 1988, A form of cytochrome P450 in man, orthologous to form d in the rat, catalyses the O-dethylation of phenacetin and is inducible by cigarette smoking. British Journal of Clinical Pharmacology, 26: 363-372.
211. Seymour, R.A. and Rawlins, M.D. 1981, Pharmacokinetics of parenteral paracetamol and its analgesic effects in post-operative dental pain. European Journal of Clinical Pharmacology, 20: 215-218.
212. Shalabi, E.A. 1992, Acetaminophen inhibits the human polymorphonuclear function in vitro. Immunopharmacology, 24: 37-46.
213. Shihabi, Z.K. and David, R.M. 1984, Colorimetric assay for acetaminophen in serum. Therapeutic Drug Monitoring, 6: 449-453.
214. Shyadehi, A.Z. and Harding, J.J. 1991, Investigations of ibuprofen and paracetamol binding to lens proteins to explore their role against cataract. Biochemical Pharmacology, 42: 2077-2084.
215. Simpson, E. and Stewart, M.J. 1973, Screening for paracetamol poisoning. Annals of Clinical Biochemistry, 10: 171.
216. Slattery, J.T. and Levy, G. 1979, Acetaminophen kinetics in acutely poisoned patients. Clinical Pharmacology and Therapeutics, 25: 184-195.
217. Slattery, J.T., McRorie, T.I., Reynolds, R., Kalhorn, T.F., Kharasch, E.D. and Eddy, A.C. 1989, Lack of effect of cimetidine on acetaminophen disposition in humans. Clinical Pharmacology and Therapeutics, 46: 591-597.
218. Slattery, J.T., Nelson, S.D. and Thummel, K.E. 1996, The complex interaction between ethanol and acetaminophen. Clinical Pharmacology and Therapeutics, 60: 241-246.
219. Slattery, J.T., Wilson, J.M., Kalhorn, T.F. and Nelson, S.D. 1987, Dose-dependent pharmacokinetics of acetaminophen: evidence of glutathione depletion in humans. Clinical Pharmacology and Therapeutics, 41: 413-418.
220. Smilgin, Z., Drozdzik, M., Gawronska-Szklarz, B., Wojcicki, J., Tustanowski, S. and Gornik, W. 1993, Pharmacokinetics of acetaminophen in individuals occupationally exposed to polyvinyl chloride modified with plasticizers. Medycyna Pracy, 44: 423-429.
221. Smith, M., Whitehead, E., O'Sullivan, G. and Reynolds, F. 1991, A comparison of serum and saliva paracetamol concentrations. British Journal of Clinical Pharmacology, 31: 553-555.
222. Smith, W.L. and Wilkin, G.P. 1977, Immunochemistry of prostaglandin endoperoxide-forming cyclooxygenase: the detection of the cyclooxygenase in rat, rabbit and guinea pig kidney by immunofluorescence. Prostaglandins, 13: 873-892.
223. Sonne, J., Boesgaard, S., Poulsen, H.E., Loft, S., Hansen, J.M., Døssing, M. and Andreasen, F. 1990, Pharmacokinetics and pharmacodynamics of oxazepam and metabolism of paracetamol in severe hypothyroidism. British Journal of Clinical Pharmacology, 30: 737-742.
224. Speck, R.F., Schranz, C. and Lauterburg, B.H. 1993, Prednisolone stimulates hepatic glutathione synthesis in mice. Protection by prednisolone against acetaminophen hepatotoxicity in vivo. Journal of Hepatology, 18: 62-67.
225. Stenken, J.A., Stahle, L., Lunte, C.E. and Southard, M.Z. 1998, Monitoring in situ liver metabolism in rats using microdialysis. Comparison of microdialysis mass-transport model predictions to experimental metabolite generation data. Journal of Pharmaceutical Sciences, 87: 311-320.
226. Stewart, M.J. and Watson, I.D. 1987, Analytical reviews in clinical chemistry: methods for the estimation of salicylate and paracetamol in serum, plasma and urine. Annals of Clinical Biochemistry, 24: 552-565.
227. Streeter, A.J., Dahlin, D.C., Nelson, S.D. and Baillie, T.A. 1984, The binding of acetaminophen to protein. Evidence for cysteine residues as major sites of arylation in vitro. Chemico-Biological Interactions, 48: 349-366.
228. Ström, C., Forsberg, O., Quiding, H., Engevall, S. and Larsson, O. 1990, Analgesic efficacy of acetaminophen sustained release. Journal of Clinical Pharmacology, 30: 654-659.
229. Studenberg, S.D. and Brouwer, K.L. 1993a, Hepatic disposition of acetaminophen and metabolites. Pharmacokinetic modeling, protein binding and subcellular distribution. Biochemical Pharmacology, 46: 739-746.
230. Studenberg, S.D. and Brouwer, K.L. 1993b, Effect of phenobarbital and p-hydroxyphenobarbital glucuronide on acetaminophen metabolites in isolated rat hepatocytes: use of a kinetic model to examine the rates of formation and egress. Journal of Pharmacokinetics and Biopharmaceutics, 21: 175-194.
231. Swaan, P.W., Marks, G.J., Ryan, F.M. and Smith, P.L. 1994, Determination of transport rates for arginine and acetaminophen in rabbit intestinal tissues in vitro. Pharmaceutical Research, 11: 283-287.
232. Teffera, Y. and Abramson, F. 1994, Application of high-performance liquid chromatography/ chemical reaction interface mass spectrometry for the analysis of conjugated metabolites: a demonstration using deuterated acetaminophen. Biological Mass Spectrometry, 23: 776-783.
233. Thomsen, M.S., Loft, S., Roberts, D.W. and Poulsen, H.E. 1995, Cytochrome P4502E1 inhibition by propylene glycol prevents acetaminophen (paracetamol) hepatotoxicity in mice without cytochrome P4501A2 inhibition. Pharmacology and Toxicology, 76: 395-399.
234. Thummel, K.E., Lee, C.A., Kunze, K.L., Nelson, S.D. and Slattery, J.T. 1993, Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinoneimine by human CYP3A4. Biochemical Pharmacology, 45: 1563-1569.
235. Thummel, K.E., Slattery, J.T. and Nelson, S.D. 1988, Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen. Journal of Pharmacology and Experimental Therapeutics, 245: 129-136.
236. Thummel, K.E., Slattery, J.T., Ro, H., Chien, J.Y., Nelson, S.D., Lown, K.E. and Watkins, P.B. 2000, Ethanol and production of the hepatotoxic metabolite of acetaminophen in healthy adults. Clinical Pharmacology and Therapeutics, 67, 591-599.
237. Tomlinson, B., Young, R.P., Ng, M.C.Y., Anderson, P.J., Kay, R. and Critchley, J.A.J.H. 1996, Selective liver enzyme induction by carbamazepine and phenytoin in Chinese epileptics. European Journal of Clinical Pharmacology, 50: 411-415.
238. Tredger, J.M., Thuluvath, P., Williams, R. and Murray-Lyon, I.M. 1995, Metabolic basis for high paracetamol dosage without hepatic damage: a case study. Human and Experimental Toxicology, 14: 8-12.
239. Tsutsumi, M., Lasker, J.M., Shimizu, M., Rosman, A.S. and Lieber, C.S. 1989, The intralobular distribution of ethanol-inducible P450IIE1 in rat and human liver. Hepatology, 10: 437-446.
240. Turner, K.C. and Brouwer, K.L. 1997, In vitro mechanisms of probenecid-associated alterations in acetaminophen glucuronide hepatic disposition. Drug Metabolism and Disposition, 25: 1017-1021.
241. van Lingen, R.A., Deinum, J.T., Quak, J.M., Kuizenga, A.J., van Dam, J.G., Anand, K.J., Tibboel, D. and Okken, A. 1999, Pharmacokinetics and metabolism of rectally administered paracetamol in preterm neonates. Archives of Disease in Children Fetal and Neonatal Edition, 80: F59-F63.
242. van Zyl, J.M., Basson, K. and van der Walt, B. 1989, The inhibitory effect of acetaminophen on the myeloperoxidase-induced antimicrobial system of the polymorphonuclear leukocyte. Biochemical Pharmacology, 38: 161-165.
243. Vance, M.V., Selden, B.S. and Clark, R.F. 1992, Optimal patient position for transport and initial management of toxic ingestions. Annals of Emergency Medicine, 21: 243-246.
244. Vendemiale, G., Altomare, E., Trizio, T., Leandro, G., Manghisi, O.G. and Albano, O. 1987, Effect of acute and chronic cimetidine administration on acetaminophen metabolism in humans. American Journal of Gastroenterology, 82: 1031-1034.
245. von Moltke, L., Manis, M., Harmatz, J.S., Poorman, R. and Greenblatt, D.J. 1993, Inhibition of acetaminophen and lorazepam glucuronidation in vitro by probenecid. Biopharmaceutics and Drug Disposition, 14: 119-130.
246. Wang, L.H., Rudolph, A.M. and Benet, L.Z. 1990, Comparative study of acetaminophen disposition in sheep at three developmental stages; the fetal, neonatal and adult periods. Developmental Pharmacology and Therapeutics, 14: 161-179.
247. West, P.R., Harman, L.S., Josephy, P.D. and Mason, R.P. 1984, Acetaminophen: enzymatic formation of a transient phenoxyl free radical. Biochemical Pharmacology, 33: 2933-2936.
248. Williams, F.M., Moore, U., Seymour, R.A., Mutch, E.M., Nicholson, E., Wright, P., Wynne, H., Blain, P.G. and Rawlins, M.D. 1989, Benorylate hydrolysis by human plasma and human liver. British Journal of Clinical Pharmacology, 28: 703-708.
249. Wilson, J.M., Slattery, J.T., Forte, A.J. and Nelson, S.D. 1982, Analysis of acetaminophen metabolites in urine by high performance liquid with UV and amperometric detection. Journal of Chromatography, 227: 453-462.
250. Wojcicki, J., Gawronska-Szklarz, B., Kazimierczyk, J., Baskiewicz, Z. and Raczynski, A. 1979, Comparative pharmacokinetics of paracetamol in men and women considering follicular and luteal phases. Arzneimittel-Forschung, 29: 350-352.
251. Wynne, H.A., Cope, L.H., Herd, B., Rawlins, M.D., James, O.F. and Woodhouse, K.W. 1990, The association of age and frailty with paracetamol conjugation in man. Age and Ageing, 19: 419-424.
252. Yan, Z., Nikelly, J.G., Killmer, L. and Tarloff, J.B. 2000, Metabolism of para-aminophenol by rat hepatocytes. Drug Metabolism and Disposition, 28: 880-886.
253. Zand, R., Nelson, S.D., Slattery, J.T., Thummel, K.E., Kalhorn, T.F., Adams, S.P. and Wright, J.M. 1993, Inhibition and induction of cytochrome P4502E1-catalyzed oxidation by isoniazid in humans. Clinical Pharmacology and Therapeutics, 54: 142-149.