Translational Research
Volume 155, Issue 6 , Pages 275-293 , June 2010

Ibuprofen-induced hypersensitivity syndrome

  • Radu M. Nanau
  • ,
  • Manuela G. Neuman

      Affiliations

    • Corresponding Author InformationReprint requests: Manuela Neuman, Department of In Vitro Drug Safety and Biotechnology, MaRS Discovery District, 101 College Street, South Tower, Lab 351, Toronto Ontario, Canada M5G 1L7

Received 1 September 2009 ,Revised 2 December 2009 ,Accepted 28 January 2010.

References 

  1. Browne GS, Nelson C, Nguyen T, Ellis BA, Day RO, Williams KM. Stereoselective and substrate-dependent inhibition of hepatic mitochondrial β-oxidation and oxidative phosphorylation by the non-steroidal anti-inflammatory drugs Ibuprofen, Flurbiprofen, and Ketorolac. Biochem Pharmacol. 1999;57:837–844
  2. Müller S, Mayer JM, Etter J-C, Testa B. Metabolic chiral inversion of Ibuprofen in isolated rat hepatocytes. Chirality. 1990;2:74–78
  3. Hamman MA, Thompson GA, Hall SD. Regioselective and stereoselective metabolism of Ibuprofen by human cytochrome P450 2C. Biochem Pharmacol. 1997;54:33–41
  4. Freneaux E, Fromenty B, Berson A, et al. Stereoselective and nonstereoselective effects of Ibuprofen enantiomers on mitochondrial -oxidation of fatty acids. J Pharmacol Exp Ther. 1990;255:529–535
  5. Schettler T, Paris S, Pellett M, Kidner S, Wilkinson D. Comparative pharmacokinetics of two fast-dissolving oral Ibuprofen formulations and a regular-release Ibuprofen tablet in healthy volunteers. Clin Drug Investig. 2001;21:73–78
  6. Rainsford KD. History and development of Ibuprofen. In:  Rainsford KD editors. Ibuprofen: a critical bibliographic review. Philadelphia, PA: Taylor & Francis; 1999;p. 1–24
  7. Rainsford KD. Pharmacology and toxicology of Ibuprofen. In:  Rainsford KD editors. Ibuprofen: a critical bibliographic review. Philadelphia, PA: Taylor & Francis; 1999;p. 143–276
  8. Halpern SM, Fitzpatrick R, Volans GN. Ibuprofen toxicity. A review of adverse reactions and overdose. Adverse Drug React Toxicol Rev. 1993;12:107–128
  9. Rodríguez-González FJ, Montero JL, Puente J, et al. Orthotopic liver transplantation after subacute liver failure induced by therapeutic doses of Ibuprofen. Am J Gastroenterol. 2002;97:2476–2477
  10. Al-Nasser IA. Ibuprofen-induced liver mitochondrial permeability transition. Toxicol Lett. 2000;111:213–218
  11. Hall SD, Rudy AC, Knight PM, Brater DC. Lack of presystemic inversion of (R)- to (S)- ibuprofen in humans. Clin Pharmacol Ther. 1993;53:393–400
  12. Mendes GD, Mendes FD, Domingues CC, et al. Comparative bioavailability of three ibuprofen formulations in healthy human volunteers. Int J Clin Pharmacol Ther. 2008;46:309–318
  13. Martin W, Koselowske G, Töberich H, Kerkmann TH, Mangold B, Augustin J. Pharmacokinetics and absolute bioavailability of Ibuprofen after oral administration of Ibuprofen lysine in man. Biopharm Drug Dispos. 1990;11:265–278
  14. Lockwood GF, Albert KS, Gillespie WR, et al. Pharmacokinetics of ibuprofen in man. I. Free and total area/dose relationship. Clin Pharmacol Ther. 1983;34:97–103
  15. Higton F. The pharmaceutics of Ibuprofen. In:  Rainsford KD editors. Ibuprofen: a critical bibliographic review. Philadelphia, PA: Taylor & Francis; 1999;p. 53–86
  16. Graham GG, Williams KM. Metabolism and pharmacokinetics of Ibuprofen. In:  Rainsford KD editors. Aspirin and related drugs. New York: Taylor & Francis; 2004;p. 157–180
  17. Bramlage P, Goldis A. Bioequivalence study of three ibuprofen formulations after single dose administration in healthy volunteers. BMC Pharmacol. 2008;8:1471–1487
  18. Doyle G, Furey S, Berlin R, et al. Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose. Aliment Pharmacol Ther. 1999;13:897–906
  19. Wood DM, Monaghan J, Streete P, Jones AL, Dargan PI. Fatality after deliberate ingestion of sustained-release ibuprofen: a case report. Crit Care. 2006;10:R44
  20. Wyeth Consumer Healthcare. Advil.com—Wyeth Consumer Healthcare. Available at: http://www.advil.com/products/advil/tablet_label.asp. Accessed August 27, 2009.
  21. Endrenyi L. Pharmacokinetics: principles and clinical application. In:  Kalant H,  Grant DM,  Mitchell J editor. Principles of medical pharmacology. 7th ed. Toronto, Canada: Elsevier; 2007;p. 50–61
  22. Mandal U, Das A, Agarwal S, et al. Bioequivalence study of two formulations containing 400 mg dexibuprofen in healthy Indian subjects. Arzneimittelforschung. 2008;58:342–347
  23. Endrenyi L. Pharmacokinetics. In:  Kalant H,  Roschlau WHE editor. Principles of medical pharmacology. 6th ed. New York: Oxford University Press; 1998;p. 55–66
  24. Nielsen JC, Bjerring P, Arendt-Nielsen L, Petterson KJ. A double-blind, placebo controlled, cross-over comparison of the analgesic effect of ibuprofen 400 mg and 800 mg on laser-induced pain. Br J Clin Pharmacol. 1990;30:711–715
  25. Greenblatt DJ, Smith TW, Koch-Weser J. Bioavailability of drugs: the digoxin dilemma. In:  Gibaldi M,  Prescott L editor. Handbook of clinical pharmacokinetics. Balgowlah, Australia: ADIS Health Science Press; 1983;p. 1–24
  26. In:  Wagner JG editors. Pharmacokinetics for the pharmaceutical scientist. Lancaster, PA: Technomics Publishing Company; 1993;
  27. Abernethy DR, Greenblatt DJ. Ibuprofen disposition in obese individuals. Arthritis Rheum. 1985;28:1117–1121
  28. In:  Hardman JG,  Limbird LE editor. Goodman and Gilman's the pharmacological basis of therapeutics. 10th ed. New York: McGraw-Hill; 2001;p. 1966
  29. Eller MG, Wright C, Della-Coletta AA. Absorption kinetics of rectally and orally administered ibuprofen. Biopharm Drug Dispos. 1989;10:269–278
  30. Zaffanello M, Brugnara M, Angeli S, Cuzzolin L. Acute non-oliguric kidney failure and cholestatic hepatitis induced by Ibuprofen and Acetaminophen: a case report. Acta Pædiatr. 2009;98:903–905
  31. Evans AM. Comparative pharmacology of S(+)-Ibuprofen and (RS)-Ibuprofen. Clin Rheumatol. 2001;1:S9–S14
  32. Evans AM, Nation RL, Sansom LN, Bochner F, Somogyi AA. The relationship between the pharmacokinetics of ibuprofen enantiomers and the dose of racemic ibuprofen in humans. Biopharm Drug Dispos. 1990;11:507–518
  33. Garabedian-Ruffalo SM, Ruffalo RL. Drug and nutrient interactions. Am Fam Physician. 1986;33:165–174
  34. Alam I, Ferrell LD, Bass NM. Vanishing bile duct syndrome temporally associated with Ibuprofen use. Am J Gastroenterol. 1996;91:1626–1630
  35. Riley TR, Smith JP. Ibuprofen-induced hepatotoxicity in patients with chronic hepatitis C: a case study. Am J Gastroenterol. 1998;93:1563–1565
  36. Gasparetto P. Un caso di ittero epatocellulare in corso di trattamento con ibuprofen (A case of hepatocellular jaundice during treatment with ibuprofen). Minerva Pediatr. 1974;26:531–533
  37. Strassburg CP, Strassburg A, Kneip S, et al. Development aspects of human hepatic drug glucuronidation in young children and adults. Gut. 2002;50:259–265
  38. Murray MD, Brater DC, Tierney WM, Hui SL, McDonald CJ. Ibuprofen-associated renal impairment in a large general internal medicine practice. Am J Med Sci. 1990;299:222–229
  39. Friis H, Andreasen PB. Drug-induced hepatic injury: an analysis of 1100 cases reported to The Danish Committee on Adverse Drug Reactions between 1978 and 1987. J Intern Med. 1992;232:133–138
  40. Sgro C, Clinard F, Ouazir K, et al. Incidence of drug-induced hepatic injury: A French population-based study. Hepatology. 2002;36:451–455
  41. Teoh NC, Farrell GC. Hepatotoxicity associated with non-steroidal anti-inflammatory drugs. Clin Liver Dis. 2003;7:401–413
  42. O'Connor N, Dargan PI, Jones AL. Hepatocellular damage from non-steroidal anti-inflammatory drugs. Q J Med. 2003;96:787–791
  43. Brocks DR, Jamali F. The pharmacokinetics of Ibuprofen in humans and animals. In:  Rainsford KD editors. Ibuprofen: A critical bibliographic review. Philadelphia, PA: Taylor & Francis; 1999;p. 87–142
  44. Boelsteli UA, Zimmerman HJ, Kretz-Rommel A. Idisyncratic liver toxicity of nonsteroidal antiinflammatory drugs: molecular mechanisms and pathology. Crit Rev Toxicol. 1995;25:207–235
  45. Tigka E, Daskala I, Rallis G, Anagnostopoulou S, Tesseromatis C. Adjuvant arthritis-induced changes on ampicillin binding in serum and tissue under the influence of non-steroidal anti-inflammatory drugs in rats. Eur J Drug Metab Pharmacokinet. 2005;30:235–241
  46. Fry SW, Seeff LB. Hepatotoxicity of analgesic and antiinflammatory agents. Gastroenterol Clin N Am. 1990;24:875–885
  47. Wood DM, Monaghan J, Streete P, Jones AL, Dargan PI. Fatality after deliberate ingestion of sustained-release ibuprofen: a case report. Crit Care. 2006;10:R44
  48. Senekjian HO, Lee CS, Kuo TH, Au DS, Krothapalli R. Absorption and disposition of ibuprofen in hemodialyzed uremic patients. Eur J Rheumatol Inflamm. 1983;6:155–162
  49. Antal EJ, Wright CE, Brown BL, Albert KS, Aman LC, Levin NW. The influence of hemodialysis on the pharmacokinetics of ibuprofen and its major metabolites. J Clin Pharmacol. 1986;26:184–190
  50. Zimmerman HJ. Update of hepatotoxicity due to classes of drugs in common clinical use: non-steroidal drugs, anti-inflammatory drugs, antibiotics, antihypertensives, and cardiac and psychotropic agents. Semin Liver Dis. 1990;10:322–338
  51. Menzel S, Waibel R, Brune K, Geisslinger G. Is the formation of R-ibuprofenyl-adenylate the first stereoselective step of chiral inversion?. Biochem Pharmacol. 1994;48:1056–1058
  52. Zheng C, Hao H, Wang G, et al. Chiral separation of ibuprofen and chiral pharmacokinetics in healthy Chinese volunteers. Eur J Drug Metab Pharmacokinet. 2008;33:45–51
  53. Chen CY, Lu PH, Chen CS. Metabolic inversion of stereoisomeric Ibuprofen in man. J Formos Med Assoc. 1991;90:437–442
  54. Desai NS, Johnston GS. Toxicity, nonsteroidal anti-inflammatory agents: eMedicine emergency medicine. Available at: http://emedicine.medscape.com/article/816117. Accessed August 29, 2009.
  55. Tracy TS, Hall SD. Metabolic inversion of (R)-Ibuprofen: epimerization and hydrolysis of ibuprofenyl-coenzyme A. Drug Metab Dispos. 1992;20:322–327
  56. Kirchheiner J, Meineke I, Freytag G, Meisel C, Roots I, Brockmöller J. Enantiospecific effects of cytochrome P450 2C9 amino acid variants on ibuprofen pharmacokinetics and on inhibition of cyclooxygenases 1 and 2. Clin Pharmacol Ther. 2002;72:62–75
  57. Jamali F, Kunz-Dober CM. Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery. Br J Clin Pharmacol. 1999;47:391–396
  58. Evans AM. Pharmacodynamics and pharmacokinetics of the Profens: enantioselectivity, clinical implications, and special reference to S(+)-Ibuprofen. J Clin Pharmacol. 1996;36:7S–15S
  59. Nichol KJ. The medicinal chemistry of Ibuprofen. In:  Rainsford KD editors. Ibuprofen: a critical bibliographic review. Philadelphia, PA: Taylor & Francis; 1999;p. 25–52
  60. Leemann TD, Transon C, Bonnabry P, Dayer P. A major role for cytochrome P450TB(CYP2C subfamily) in the actions of non-steroidal antiinflammatory drugs. Drugs Exp Clin Res. 1993;19:189–195
  61. Chen CY, Chen CS. Stereoselective disposition of Ibuprofen in patients with renal dysfunction. The J Pharmacol Exp Ther. 1994;268:590–594
  62. Tulaganov AA, Volchenok VI, Kukes VG, Arzamastsev AP. Clinical pharmacokinetics of Ibuprofen. J Med Pharm Chem. 1993;27:21–24
  63. Chen CY, Chen CS. Stereoselective disposition of ibuprofen in patients with compromised renal haemodynamics. J Clin Pharmacol. 1995;40:67–72
  64. Schmitt M, Guentert TW. Effect of age on the pharmacokinetics of Tenoxicam in comparison to other non-steroidal anti-inflammatory drugs (NSAIDS). Scand J Rheumatol Suppl. 1989;18:86–89
  65. Kotlyar M, Carson SW. Effects of obesity on the cytochrome P450 enzyme system. Int J Clin Pharmacol Ther. 1999;37:8–19
  66. Bowdle TA, Neal GD, Levy RH, Heimbach DM. Phenytoin pharmacokinetics in burned rats and plasma protein binding of phenytoin in burned patients. J Pharmacol Exp Ther. 1980;213:97–99
  67. Petric M, Tasic L, Sukljevic S. Nonsteroidal anti-inflammatory drug usage and gastrointestinal outcomes in the Republic of Serbia. J Pain Palliat Care Pharmacother. 2009;23:40–47
  68. Neuman MG, Malkiewicz IM, Shear NH. A novel lymphocyte toxicity assay to assess drug hypersensitivity syndrome. Clin Biochem. 2000;33:517–524
  69. Hall AH, Smolinske SC, Conrad FL, et al. Ibuprofen overdose: 126 cases. Ann Emerg Med. 1986;15:1308–1313
  70. Öker EE, Hermann L, Baum CR, Fentzke KM, Sigg T, Leikin JB. Serious toxicity in a young child due to Ibuprofen. Acad Emerg Med. 2000;7:821–823
  71. Downie A, Ali A, Bell D. Severe metabolic acidosis complicating massive ibuprofen overdose. Postgrad Med J. 1993;69:575–577
  72. Seifert SA, Bronstein AC, McGuire T. Massive Ibuprofen ingestion with survival. J Toxicol Clin Toxicol. 2000;38:55–57
  73. Pessayre D. Role of reactive metabolites in drug-induced hepatitis. J Hepatol. 1995;23:16–24
  74. Krivoy N, Taeri M, Neuman MG. Antiepileptic drug-induced hypersensitivity syndrome reactions. Curr Drug Saf. 2006;1:289–299
  75. Neuman MG, Nicar M. Apoptosis in ibuprofen-induced Stevens–Johnson syndrome. Trans Res. 2007;149:254–259
  76. Neuman MG, Shear NH, Malkiewicz IM, et al. Immunopathogenesis of hypersensitivity syndrome reactions to sulfonamides. Trans Res. 2007;149:243–253
  77. Srivastava M, Perez-Atayde A, Jonas MM. Drug-associated acute-onset vanishing bile duct and Stevens-Johnson Syndromes in a child. Gastroenterology. 1998;115:743–746
  78. Chung WH, Hung SI, Chen YT. Human leukocyte antigens and drug hypersensitivity. Curr Opin Allergy Clin Immunol. 2007;7:317–323
  79. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. N Engl J Med. 1995;333:1600–1607
  80. Halevy S, Ghislain PD, Mockenhaupt M, et al. Allopurinol is the most common cause of Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol. 2008;58:25–32
  81. Mockenhaupt M, Viboud C, Dunant A, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis: assessment of medication risks with emphasis on recently marketed drugs. The EuroSCAR-study. J Invest Dermatol. 2008;128:35–44
  82. Posadas SJ, Pichler WJ. Delayed drug hypersensitivity reactions—new concepts. Clin Exp Allergy. 2007;37:989–999
  83. Jurima-Romet M, Crawford K, Huang HS. Comparative cytotoxicity of non-steroidal anti-inflammatory drugs in primary cultures of rat hepatocytes. Toxicol In Vitro. 1994;8:55–66
  84. Leeder JS, Cannon M, Nakhooda A, Spielberg SP. Drug metabolite toxicity assessed in human lymphocytes with a purified, reconstituted cytochrome P450 system. J Pharmacol Exp Ther. 1988;245:956–962
  85. Beeler A, Engler O, Gerber BO, Pichler WJ. Long-lasting reactivity and high frequency of drug-specific T cells after severe systemic drug hypersensitivity reactions. J Allergy Clin Immunol. 2006;117:455–462
  86. Vassalli P. The pathophisiology of tumor necrosis factors. Annu Rev Immunol. 1992;10:411–452
  87. Ertel W, Morrison MH, Ayala A, Chaudry IH. Eicosanoids regulate tumor necrosis factor synthesis after hemorrhage in vitro and in vivo. J Trauma. 1991;31:609–616
  88. Wanner GA, Müller P, Ertel W, Busch CJ, Menger MD, Messmer K. Differential effect of cyclooxygenase metabolites on proinflammatory cytokine release by Kupffer cells after liver ischemia and reperfusion. Am J Surg. 1998;175:146–151
  89. Mascagni P, Sabbatini V, Biordi L, et al. R- and S-isomers of nonsteroidal anti-inflammatory drugs differentially regulate cytokine production. Eur Cytokine Netw. 2000;11:185–192
  90. Chitturi S, George J. Hepatotoxicity of commonly used drugs: monsteroidal anti-inflammatory drugs, antihypertensives, antidiabetic agents, anticonvulsants, lipid-lowering agents, phychotropic drugs. Semin Liver Dis. 2002;22:169–183
  91. Castell JV, Larrauri L, Gómez-Lechón MJ. A study of relative hepatotoxicity in vitro of the non-steroidal anti-inflammatory drugs ibuprofen, flurbiprofen and butibufen. Xenobiotica. 1988;18:737–745
  92. Rabinovitz M, Van Thiel DH. Hepatotoxicity of nonsteroidal anti-inflammatory drugs. Am J Gastroenterol. 1992;87:1696–1704
  93. Walker AM. Quantitative studies of the risk of serious hepatic injury in persons using nonsteroidal anti-inflammatory drugs. Arthritis Rheum. 1997;40:201–208
  94. Rodríguez LAG, Williams R, Derby LE, Dean AD, Jick H. Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors. Arch Intern Med. 1994;154:311–316
  95. Turner WM. The Food and Drug Administration algorithm special workshop –regulatory. Drug Inf J. 1984;18:259–266
  96. Shear NH. Diagnosing cutaneous adverse reactions to drugs. Arch Dermatol. 1990;126:94–97
  97. Bravo JF, Jacobson MP, Mertens BF. Fatty liver and pleural effusion with Ibuprofen therapy. Ann Intern Med. 1977;87:200–201
  98. Stempel DA, Miller JJ. Lymphopenia and hepatic toxicity with ibuprofen. J Pediatr. 1977;90:657–658
  99. Laurent S, Rahier J, Geubel AP, Lerut J, Horsmans Y. Subfulminant hepatitis requiring liver transplantation following ibuprofen overdose. Liver. 2000;20:93–94
  100. Taghian M, Tran TA, Bresson-Hadni S, Menget A, Felix S, Jacquemin E. Acute vanishing bile duct syndrome after Ibuprofen therapy in a child. J Pediatr. 2004;145:273–276
  101. Sternleib P, Robinson RM. Stevens-Johnson syndrome plus toxic hepatitis due to ibuprofen. NY State J Med. 1978;87:200–202
  102. Lee CY, Finkler A. Acute intoxication due to ibuprofen overdose. Arch Pathol Lab Med. 1986;110:747
  103. Borel I, Hedelius F, Baumgartner C, Vial T, Scoazec JY, Dumortier J. Severe acute hepatitis associated with ibuprofen treatment. Gastroentérol Clin Biol. 2001;25:430
  104. Reinicke C, Klinger W. Influence of ibuprofen on drug-metabolizing enzymes in rat liver in vivo and in vitro. Biochem Pharmacol. 1975;24:145–147
  105. Bendele AM, Hulman JF, White S, Brodhecker C, Bendele RA. Hepatocellular proliferation in Ibuprofen-treated mice. Toxicol Pathol. 1993;21:15–20
  106. Rekka E, Ayalogu EO, Lewis DFV, Gibson GG, Ioannides C. Induction of hepatic microsomal CYP4A activity and of peroxisomal -oxidation by two non-steroidal anti-inflammatory drugs. Arch Toxicol. 1994;68:73–78
  107. Sternlieb P, Robinson RM. Stevens-Johnson Syndrome plus toxic hepatitis due to Ibuprofen. NY State J Med. 1978;78:1239–1243
  108. Chitturi S, Farrell GC. Drug-induced cholestasis. Semin Gastrointest Dis. 2001;12:113–124
  109. Morelli MS, O'Brien FX. Stevens-Johnson Syndrome and cholestatic hepatitis. Dig Dis Sci. 2001;46:2385–2388
  110. Hurwitz RM, Rivera HP, Gooch MH, Stama TG, Handt A, Weiss J. Toxic shock syndrome or toxic epidermal necrolysis? Case reports showing clinical similarity and histologic separation. J Am Acad Dermatol. 1982;7:246–254
  111. Neuman MG, Monteiro M, Rehm J. Drug interactions between psychoactive Substances and antiretroviral therapy in individuals infected with human immunodeficiency and Hepatitis viruses. Subst Use Misuse. 2006;41:1395–1463
  112. Neuman MG, Peng P, Betschel SD. Immune mediated drug hypersensitivity reactions to hydromorphone. Eur J Dermatol. 2008;18:250
  113. Neuman MG, Shear NH, Gomez M, et al. Cytokines-chemokines and hypersensitivity syndrome reactions to ibuprofen. Eur J Dermatol. 2008;18:269–270
  114. Lonjou C, Thomas L, Borot N, et al. A marker for Stevens-Johnson syndrome- ethnicity matters. Pharmacogenomics J. 2006;6:265–268
  115. Dore J, Salisbury RE. Morbidity and mortality of mucocutaneous diseases in the pediatric population at a tertiary care center. J Burn Care Res. 2007;28:865–870
  116. Ueta M, Sotozono C, Tokunaga K, Yabe T, Kinoshita S. Strong association between HLA-A0206 and Stevens-Johnson syndrome in the Japanese. Am J Ophthalmol. 2007;143:367–368
  117. Layton D, Marshal V, Boshier A, Friedmann P, Shakir SAW. Serious skin reactions andselective COX-2 inhibitors: A case series from prescription-event monitoring in England. Drug Saf. 2006;29:687–696
  118. Neuman MG, Shear N, Gomez M, et al. Hypersensitivity reaction to Ibuprofen. Ther Drug Monit. 2009;31:5,77,626
  119. Yoshimura T, Kurita C, Hayata M, Nagai H. Diagnosis of drug allergy by the lymphocyte stimulation test with the MTT [3-(4,5-dimethyl thiazol-2-yl)-2,5-diophenyl tetrazolium bromide] assay. Biol Pharm Bull. 1993;16:686–689
  120. Chissov VI, Sviridova IK, Sergeeva NS, et al. In vitro study of matrix surface properties of porous granulated calcium phosphate ceramic materials made in Russia. Bull Exp Biol Med. 2008;145:499–503
  121. Berns M, Toennessen M, Koehne P, Altmann R, Obladen M. Ibuprofen augments bilirubin toxicity in rat cortical neuronal culture. Pediatr Res. 2009;65:392–396
  122. Nassif A, Moslehi H, Le Gouvello S, et al. Evaluation of the potential role of cytokines in toxic epidermal necrolysis. J Invest Dermatol. 2004;123:850–855
  123. McElwee NE, Veltri JC, Bradford DC, Rollins DE. A prospective, population-based study of acute ibuprofen overdose: complications are rare and routine serum levels not warranted. Ann Emerg Med. 1990;19:657–662
  124. Al-Meshal MA, El-Sayed YM, Al-Balla SR, Gouda MW. The effect of Colestipol and Cholestyramine on Ibuprofen bioavailability in man. Biopharm Drug Dispos. 1994;15:463–471
  125. Knights KM, Addinall TF, Roberts BJ. Enhanced chiral inversion of R-ibuprofen in liver from rats treated with clofibric acid. Biochem Pharmacol. 1991;41:1775–1777
  126. Solomon DH, Goodson NJ. The cardiovascular system in rheumatic disease: the newest “extraarticular” manifestation?. J Rheumatol. 2005;32:1415–1419

PII: S1931-5244(10)00030-7

doi: 10.1016/j.trsl.2010.01.005

Translational Research
Volume 155, Issue 6 , Pages 275-293 , June 2010