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Clinical use and pharmacological properties of selective COX-2 inhibitors

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Abstract

Selective COX-2 inhibitors (coxibs) are approved for the relief of acute pain and symptoms of chronic inflammatory conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA). They have similar pharmacological properties but a slightly improved gastrointestinal (GI) safety profile if compared to traditional nonsteroidal anti-inflammatory drugs (tNSAIDs). However, long-term use of coxibs can be associated with an increased risk for cardiovascular (CV) adverse events (AEs). For this reason, two coxibs were withdrawn from the market. Currently celecoxib, etoricoxib, and lumiracoxib are used. These three coxibs differ in their chemical structure and selectivity for COX-2, which might explain some of their pharmacological features. Following oral administration, the less lipophilic celecoxib has a lower bioavailability (20–40%) than the other two coxibs (74–100%). All are eliminated by hepatic metabolism involving mainly CYP2C9 (celecoxib, lumiracoxib) and CYP3A4 (etoricoxib). Elimination half-life varies from 5 to 8 h (lumiracoxib), 11 to 16 h (celecoxib) and 19 to 32 h (etoricoxib). In patients with liver disease, plasma levels of celecoxib and etoricoxib are increased about two-fold. Clinical efficacies of the coxibs are comparable to tNSAIDs. There is an ongoing discussion about whether the slightly better GI tolerability (which is lost if acetylsalicylic acid is coadministered) of the coxibs is offset by their elevated risks for CV AEs (also seen with tNSAIDs other than naproxen), which apparently increase with dose and duration of exposure. In addition, the higher costs for coxibs (if compared to tNSAIDs, even when a “gastroprotective” proton pump inhibitor is coadministered) should be taken into consideration, if a coxib will be selected for certain patients with a high risk for GI complications. For such treatment, the lowest effective dose should be used for a limited time. Monitoring of kidney function and blood pressure appears advisable. It is hoped that further controlled studies can better define the therapeutic place of the coxibs.

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References

  1. Vane JR, Flower RJ, Botting RM (1990) History of aspirin and its mechanism of action. Stroke 21(Suppl 12):IV12–IV23

    PubMed  CAS  Google Scholar 

  2. Wallace JL (1997) Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 112:1000–1016

    PubMed  CAS  Google Scholar 

  3. Wolfe MM, Lichtenstein DR, Singh G (1999) Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 340:1888–1899

    PubMed  CAS  Google Scholar 

  4. Scheiman JM (2006) Unmet needs in non-steroidal anti-inflammatory drug-induced upper gastrointestinal diseases. Drugs 66(Suppl 1):15–21, discussion 29–33

    PubMed  CAS  Google Scholar 

  5. Vane JR (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 231:232–235

    PubMed  CAS  Google Scholar 

  6. Seibert K, Masferrer J, Zhang Y, Gregory S, Olson G, Hauser S, Leahy K, Perkins W, Isakson P (1995) Mediation of inflammation by cyclooxygenase-2. Agents Actions Suppl 46:41–50

    PubMed  CAS  Google Scholar 

  7. Capone ML, Tacconelli S, Di Francesco L, Sacchetti A, Sciulli MG, Patrignani P (2007) Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat 82:85–94

    PubMed  CAS  Google Scholar 

  8. Ruschitzka F (2007) Painful lessons: COX-2 inhibitors, NSAIDs, and hypertension. Curr Hypertens Rep 9:41–44

    PubMed  Google Scholar 

  9. Psaty BM, Furberg CD (2005) COX-2 inhibitors-lessons in drug safety. N Engl J Med 352:1133–1135

    PubMed  CAS  Google Scholar 

  10. Maxwell SR, Webb DJ (2005) COX-2 selective inhibitors-important lessons learned. Lancet 365:449–451

    PubMed  Google Scholar 

  11. Sooriakumaran P (2006) COX-2 inhibitors and the heart: are all coxibs the same? Postgrad Med J 82:242–245

    PubMed  CAS  Google Scholar 

  12. Araujo LF, Soeiro Ade M, Fernandes Jde L, Serrano Júnior CV (2005) Cardiovascular events: a class effect by COX-2 inhibitors. Arq Bras Cardiol 85:222–229

    PubMed  CAS  Google Scholar 

  13. Tacconelli S, Capone ML, Patrignani P (2004) Clinical pharmacology of novel selective COX-2 inhibitors. Curr Pharm Des 10:589–601

    PubMed  CAS  Google Scholar 

  14. Praticò D, Dogné JM (2005) Selective cyclooxygenase-2 inhibitors development in cardiovascular medicine. Circulation 112:1073–1079

    PubMed  Google Scholar 

  15. Guzmán HR, Tawa M, Zhang Z, Ratanabanangkoon P, Shaw P, Gardner CR, Chen H, Moreau JP, Almarsson O, Remenar JF (2007) Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. J Pharm Sci 96:2686–2702

    PubMed  Google Scholar 

  16. Brune K, Hinz B (2004) Selective cyclooxygenase-2 inhibitors: similarities and differences. Scand J Rheumatol 33(1):1–6

    Article  PubMed  CAS  Google Scholar 

  17. Paulson SK, Hribar JD, Liu NW, Hajdu E, Bible RH, Piergies A, Karim A (2000) Metabolism and excretion of [(14)C] celecoxib in healthy male volunteers. Drug Metab Dispos 28:308–314

    PubMed  CAS  Google Scholar 

  18. Babu GVMM, Shankar VG, Sankar KH, Seshasayana A, Kumar NK, Murthy KVR (2002) Development of dissolution medium for a poorly water soluble drug, celecoxib. Indian J Pharm Sci 6:588–590

    Google Scholar 

  19. Paulson SK, Vaughn MB, Jessen SM, Lawal Y, Gresk CJ, Yan B, Maziasz TJ, Cook CS, Karim A (2001) Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. J Pharmacol Exp Ther 297:638–645

    PubMed  CAS  Google Scholar 

  20. Gardiner SJ, Doogue MP, Zhang M, Begg EJ (2004) Quantification of infant exposure to celecoxib through breast milk. Br J Clin Pharmacol 61:101–104

    Google Scholar 

  21. Hale TW, McDonald R, Boger J (2004) Transfer of celecoxib into human milk. J Hum Lact 20:397–403

    PubMed  Google Scholar 

  22. Kirchheiner J, Störmer E, Meisel C, Steinbach N, Roots I, Brockmöller J (2003) Influence of CYP2C9 genetic polymorphisms on pharmacokinetics of celecoxib and its metabolites. Pharmacogenetics 13:473–480

    PubMed  CAS  Google Scholar 

  23. Tang C, Shou M, Mei Q, Rushmore TH, Rodrigues AD (2000) Major role of human liver microsomal cytochrome P450 2C9 (CYP2C9) in the oxidative metabolism of celecoxib, a novel cyclooxygenase-II inhibitor. J Pharmacol Exp Ther 293:453–459

    PubMed  CAS  Google Scholar 

  24. Itthipanichpong C, Chompootaweep S, Wittayalertpanya S, Kemsri W, Thaworn N, Lilitkarntrakul P, Parikamsil S (2005) Clinical pharmacokinetic of celecoxib in healthy Thai volunteers. J Med Assoc Thai 88:632–638

    PubMed  Google Scholar 

  25. Rodrigues AD, Yang Z, Chen C, Pray D, Kim S, Sinz M (2006) Is celecoxib an inducer of cytochrome P450 3A4 in subjects carrying the CYP2C9*3 allele? Clin Pharmacol Ther 80:298–301

    PubMed  CAS  Google Scholar 

  26. Stempak D, Bukaveckas BL, Linder M, Koren G, Baruchel S (2005) Cytochrome P450 2C9 genotype: impact on celecoxib safety and pharmacokinetics in a pediatric patient. Clin Pharmacol Ther 78:309–310

    PubMed  CAS  Google Scholar 

  27. Lundblad MS, Ohlsson S, Johansson P, Lafolie P, Eliasson E (2006) Accumulation of celecoxib with a 7-fold higher drug exposure in individuals homozygous for CYP2C9*3. Clin Pharmacol Ther 79:287–288

    PubMed  CAS  Google Scholar 

  28. Rodrigues AD (2005) Impact of CYP2C9 genotype on pharmacokinetics: are all cyclooxygenase inhibitors the same? Drug Metab Dispos 33:1567–1575

    PubMed  CAS  Google Scholar 

  29. Tang C, Shou M, Rushmore TH, Mei Q, Sandhu P, Woolf EJ, Rose MJ, Gelmann A, Greenberg HE, De Lepeleire I, Van Hecken A, De Schepper PJ, Ebel DL, Schwartz JI, Rodrigues AD (2001) In-vitro metabolism of celecoxib, a cyclooxygenase-2 inhibitor, by allelic variant forms of human liver microsomal cytochrome P450 2C9: correlation with CYP2C9 genotype and in-vivo pharmacokinetics. Pharmacogenetics 11:223–235

    PubMed  CAS  Google Scholar 

  30. Brenner SS, Herrlinger C, Dilger K, Mürdter TE, Hofmann U, Marx C, Klotz U (2003) Influence of age and cytochrome P450 2C9 genotype on the steady-state disposition of diclofenac and celecoxib. Clin Pharmacokinet 42:283–292

    PubMed  CAS  Google Scholar 

  31. Pilotto A, Seripa D, Franceschi M, Scarcelli C, Colaizzo D, Grandone E, Niro V, Andriulli A, Leandro G, Di Mario F, Dallapiccola B (2007) Genetic susceptibility to nonsteroidal anti-inflammatory drug-related gastroduodenal bleeding: role of cytochrome P450 2C9 polymorphisms. Gastroenterology 133:465–471

    PubMed  CAS  Google Scholar 

  32. Stempak D, Gammon J, Klein J, Koren G, Baruchel S (2002) Single-dose and steady-state pharmacokinetics of celecoxib in children. Clin Pharmacol Ther 72:490–497

    PubMed  CAS  Google Scholar 

  33. Blanco JG, Harrison PL, Evans WE, Relling MV (2000) Human cytochrome P450 maximal activities in pediatric versus adult liver. Drug Metab Dispos 28(4):379–382

    PubMed  CAS  Google Scholar 

  34. Stempak D, Gammon J, Halton J, Champagne M, Koren G, Baruchel S (2005) Modulation of celecoxib pharmacokinetics by food in pediatric patients. Clin Pharmacol Ther 77:226–228

    PubMed  CAS  Google Scholar 

  35. Dentali F, Douketis JD, Woods K, Thabane L, Foster G, Holbrook A, Crowther M (2006) Does celecoxib potentiate the anticoagulant effect of warfarin? A randomized, double-blind, controlled trial. Ann Pharmacother 40:1241–1247

    PubMed  CAS  Google Scholar 

  36. Karim A, Tolbert DS, Hunt TL, Hubbard RC, Harper KM, Geis GS (1999) Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol 26:2539–2543

    PubMed  CAS  Google Scholar 

  37. Davies NM, McLachlan AJ, Day RO, Williams KM (2000) Clinical pharmacokinetics and pharmacodynamics of celecoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 38:225–242

    PubMed  CAS  Google Scholar 

  38. Phelan KM, Mosholder AD, Lu S (2003) Lithium interaction with the cyclooxygenase 2 inhibitors rofecoxib and celecoxib and other nonsteroidal anti-inflammatory drugs. J Clin Psychiatry 64:1328–1334

    Article  PubMed  CAS  Google Scholar 

  39. Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K (2003) Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. Clin Pharmacol Ther 74:130–137

    PubMed  CAS  Google Scholar 

  40. Jayasagar G, Krishna Kumar M, Chandrasekhar K, Madhusudan Rao Y (2003) Influence of rifampicin pretreatment on the pharmacokinetics of celecoxib in healthy male volunteers. Drug Metabol Drug Interact 19:287–295

    PubMed  CAS  Google Scholar 

  41. Saxena AK, Ramachandran R, Gulati M, Kumar M (2005) Cyclooxygenase-2 inhibitors in postoperative pain and chronic pain management: current opinions and future perspectives. Indian J Anaesth 49:170–179

    Google Scholar 

  42. Agrawal NG, Porras AG, Matthews CZ, Woolf EJ, Miller JL, Mukhopadhyay S, Neu DC, Gottesdiener KM (2001) Dose proportionality of oral etoricoxib, a highly selective cyclooxygenase-2 inhibitor, in healthy volunteers. J Clin Pharmacol 41:1106–1110

    PubMed  CAS  Google Scholar 

  43. Agrawal NG, Porras AG, Matthews CZ, Rose MJ, Woolf EJ, Musser BJ, Dynder AL, Mazina KE, Lasseter KC, Hunt TL, Schwartz JI, McCrea JB, Gottesdiener KM (2003) Single- and multiple-dose pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, in man. J Clin Pharmacol 43:268–276

    PubMed  CAS  Google Scholar 

  44. Rodrigues AD, Halpin RA, Geer LA, Cui D, Woolf EJ, Matthews CZ, Gottesdiener KM, Larson PJ, Lasseter KC, Agrawal NG (2003) Absorption, metabolism, and excretion of etoricoxib, a potent and selective cyclooxygenase-2 inhibitor, in healthy male volunteers. Drug Metab Dispos 31:224–232

    PubMed  CAS  Google Scholar 

  45. Kassahun K, McIntosh IS, Shou M, Walsh DJ, Rodeheffer C, Slaughter DE, Geer LA, Halpin RA, Agrawal N, Rodrigues AD (2001) Role of human liver cytochrome P4503A in the metabolism of etoricoxib, a novel cyclooxygenase-2 selective inhibitor. Drug Metab Dispos 29:813–820

    PubMed  CAS  Google Scholar 

  46. Agrawal NG, Matthews CZ, Mazenko RS, Woolf EJ, Porras AG, Chen X, Miller JL, Michiels N, Wehling M, Schultz A, Gottlieb AB, Kraft WK, Greenberg HE, Waldman SA, Curtis SP, Gottesdiener KM (2004) The effects of modifying in vivo cytochrome P450 3A (CYP3A) activity on etoricoxib pharmacokinetics and of etoricoxib administration on CYP3A activity. J Clin Pharmacol 44:1125–1131

    PubMed  CAS  Google Scholar 

  47. Schwartz JI, Agrawal NG, Hartford AH, Cote J, Hunt TL, Verbesselt R, Eckols DR, Gottesdiener KM (2007) The effect of etoricoxib on the pharmacodynamics and pharmacokinetics of warfarin. J Clin Pharmacol 47:620–627

    PubMed  CAS  Google Scholar 

  48. Agrawal NG, Matthews CZ, Mazenko RS, Kline WF, Woolf EJ, Porras AG, Geer LA, Wong PH, Cho M, Cote J, Marbury TC, Moncrief JW, Alcorn H, Swan S, Sack MR, Robson RA, Petty KJ, Schwartz JI, Gottesdiener KM (2004) Pharmacokinetics of etoricoxib in patients with renal impairment. J Clin Pharmacol 44:48–58

    PubMed  CAS  Google Scholar 

  49. Agrawal NG, Rose MJ, Matthews CZ, Woolf EJ, Porras AG, Geer LA, Larson PJ, Cote J, Dilzer SC, Lasseter KC, Alam I, Petty KJ, Gottesdiener KM (2003) Pharmacokinetics of etoricoxib in patients with hepatic impairment. J Clin Pharmacol 43:1136–1148

    PubMed  CAS  Google Scholar 

  50. Mangold JB, Gu H, Rodriguez LC, Bonner J, Dickson J, Rordorf C (2004) Pharmacokinetics and metabolism of lumiracoxib in healthy male subjects. Drug Metab Dispos 32:566–571

    PubMed  CAS  Google Scholar 

  51. Scott G, Rordorf C, Blood P, Branson J, Milosavljev S, Greig G (2002) Dose escalation study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of COX189 in healthy subjects. Ann Rheum Dis 61(Suppl 1):242(Abstract FRI0300)

    Google Scholar 

  52. Scott G, Branson J, Milosavljev S, Rordorf C, Haraoui B, Ouellet J-P (2003) Lumiracoxib demonstrates dose-proportional and time-independent pharmacokinetics in patients with osteoarthritis of the knee. Ann Rheum Dis 62(Suppl 1):267(Abstract FRI0235)

    Google Scholar 

  53. Scott G, Rordorf C, Reynolds C, Kalbag J, Looby M, Milosavljev S, Weaver M, Huff JP, Ruff DA (2004) Pharmacokinetics of lumiracoxib in plasma and synovial fluid. Clin Pharmacokinet 43:467–478

    PubMed  CAS  Google Scholar 

  54. Rordorf CM, Choi L, Marshall P, Mangold JB (2005) Clinical pharmacology of lumiracoxib: a selective cyclo-oxygenase-2 inhibitor. Clin Pharmacokinet 44:1247–1266

    PubMed  CAS  Google Scholar 

  55. Esser R, Berry C, Du Z, Dawson J, Fox A, Fujimoto RA, Haston W, Kimble EF, Koehler J, Peppard J, Quadros E, Quintavalla J, Toscano K, Urban L, van Duzer J, Zhang X, Zhou S, Marshall PJ (2005) Preclinical pharmacology of lumiracoxib: a novel selective inhibitor of cyclooxygenase-2. Br J Pharmacol 144:538–550

    PubMed  CAS  Google Scholar 

  56. Jermany J, Branson J, Schmouder R, Guillaume M, Rordorf C (2005) Lumiracoxib does not affect the ex vivo antiplatelet aggregation activity of low-dose aspirin in healthy subjects. J Clin Pharmacol 45:1172–1178

    PubMed  CAS  Google Scholar 

  57. Scott G, Yih L, Yeh CM, Milosavljev S, Laurent A, Rordorf C (2004) Lumiracoxib: pharmacokinetic and pharmacodynamic profile when coadministered with fluconazole in healthy subjects. J Clin Pharmacol 44:193–199

    PubMed  CAS  Google Scholar 

  58. Scott G, Vinluan Reynolds C, Milosavljev S, Langholff W, Shenouda M, Rordorf C (2004) Lack of effect of omeprazole or of an aluminium hydroxide/magnesium hydroxide antacid on the pharmacokinetics of lumiracoxib. Clin Pharmacokinet 43:341–348

    PubMed  CAS  Google Scholar 

  59. Hartmann SN, Rordorf CM, Milosavljev S, Branson JM, Chales GH, Juvin RR, Lafforgue P, Le Parc JM, Tavernier CG, Meyer OC (2004) Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients. Ann Pharmacother 38:1582–1587

    PubMed  CAS  Google Scholar 

  60. Buvanendran A, Barkin R (2007) Lumiracoxib. Drugs Today (Barc) 43:137–147

    CAS  Google Scholar 

  61. Kalbag J, Yeh CM, Milosavljev S, Lasseter K, Oberstein S, Rordorf C (2004) No influence of moderate hepatic impairment on the pharmacokinetics of lumiracoxib, an oral COX-2 selective inhibitor. Pharmacol Res 50:181–186

    PubMed  CAS  Google Scholar 

  62. O’Banion MK, Sadowski HB, Winn V, Young DA (1991) A serum- and glucocorticoid-regulated 4-kilobase mRNA encodes a cyclooxygenase-related protein. J Biol Chem 266:23261–23267

    PubMed  CAS  Google Scholar 

  63. Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR (1991) TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266:12866–12872

    PubMed  CAS  Google Scholar 

  64. Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL (1991) Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci USA 88:2692–2696

    PubMed  CAS  Google Scholar 

  65. Masferrer JL, Zweifel BS, Manning PT, Hauser SD, Leahy KM, Smith WG, Isakson PC, Seibert K (1994) Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic. Proc Natl Acad Sci USA 91:3228–3232

    PubMed  CAS  Google Scholar 

  66. de Leval X, Hanson J, David JL, Masereel B, Pirotte B, Dogné JM (2004) New developments on thromboxane and prostacyclin modulators. Part II: prostacyclin modulators. Curr Med Chem 11:1243–1252

    PubMed  CAS  Google Scholar 

  67. Taniura S, Kamitani H, Watanabe T, Eling TE (2002) Transcriptional regulation of cyclooxygenase-1 by histone deacetylase inhibitors in normal human astrocyte cells. J Biol Chem 277:16823–16830

    PubMed  CAS  Google Scholar 

  68. FitzGerald GA, Patrono C (2001) The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med 345:433–442

    PubMed  CAS  Google Scholar 

  69. FitzGerald GA (2002) Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: clinical considerations. Am J Cardiol 89:26D–32D

    PubMed  CAS  Google Scholar 

  70. Dogné JM, de Leval X, Hanson J, Frederich M, Lambermont B, Ghuysen A, Casini A, Masereel B, Ruan KH, Pirotte B, Kolh P (2004) New developments on thromboxane and prostacyclin modulators. Part I: thromboxane modulators. Curr Med Chem 11:1223–1241

    PubMed  Google Scholar 

  71. Grosser T, Fries S, FitzGerald GA (2006) Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest 116:4–15

    PubMed  CAS  Google Scholar 

  72. Fries S, Grosser T (2005) The cardiovascular pharmacology of COX-2 inhibition. Hematol Am Soc Hematol Educ Program 2005:445–451

  73. Kraemer SA, Meade EA, DeWitt DL (1992) Prostaglandin endoperoxide synthase gene structure: identification of the transcriptional start site and 5″-flanking regulatory sequences. Arch Biochem Biophys 293:391–400

    PubMed  CAS  Google Scholar 

  74. Topol EJ, Falk GW (2004) A coxib a day won’t keep the doctor away. Lancet 364:639–640

    PubMed  Google Scholar 

  75. Petrella R, Ekman EF, Schuller R, Fort JG (2004) Efficacy of celecoxib, a COX-2-specific inhibitor, and naproxen in the management of acute ankle sprain: results of a double-blind, randomized controlled trial. Clin J Sport Med 14:225–231

    PubMed  Google Scholar 

  76. Bertin P, Béhier JM, Noël E, Leroux JL (2003) Celecoxib is as efficacious as naproxen in the management of acute shoulder pain. J Int Med Res 31:102–112

    PubMed  CAS  Google Scholar 

  77. Salo DF, Lavery R, Varma V, Goldberg J, Shapiro T, Kenwood A (2003) A randomized, clinical trial comparing oral celecoxib 200 mg, celecoxib 400 mg, and ibuprofen 600 mg for acute pain. Acad Emerg Med 10:22–30

    Article  PubMed  Google Scholar 

  78. Ekman EF, Fiechtner JJ, Levy S, Fort JG (2002) Efficacy of celecoxib versus ibuprofen in the treatment of acute pain: a multicenter, double-blind, randomized controlled trial in acute ankle sprain. Am J Orthop 31:445–451

    PubMed  Google Scholar 

  79. Nikanne E, Kokki H, Salo J, Linna TJ (2005) Celecoxib and ketoprofen for pain management during tonsillectomy: a placebo-controlled clinical trial. Otolaryngol Head Neck Surg 132:287–294

    PubMed  Google Scholar 

  80. Reuben SS, Ekman EF, Charron D (2007) Evaluating the analgesic efficacy of administering celecoxib as a component of multimodal analgesia for outpatient anterior cruciate ligament reconstruction surgery. Anesth Analg 105:222–227

    PubMed  CAS  Google Scholar 

  81. Reuben SS, Buvanendran A, Kroin JS, Raghunathan K (2006) The analgesic efficacy of celecoxib, pregabalin, and their combination for spinal fusion surgery. Anesth Analg 103:1271–1277

    PubMed  CAS  Google Scholar 

  82. Ekman EF, Wahba M, Ancona F (2006) Analgesic efficacy of perioperative celecoxib in ambulatory arthroscopic knee surgery: a double-blind, placebo-controlled study. Arthroscopy 22:635–642

    Article  PubMed  Google Scholar 

  83. Zemmel MH (2006) The role of COX-2 inhibitors in the perioperative setting: efficacy and safety-a systematic review. AANA J 74:49–60

    PubMed  Google Scholar 

  84. Malmstrom K, Sapre A, Couglin H, Agrawal NG, Mazenko RS, Fricke JR (2004) Etoricoxib in acute pain associated with dental surgery: a randomized, double-blind, placebo- and active comparator-controlled dose-ranging study. Clin Ther 26:667–679

    PubMed  CAS  Google Scholar 

  85. Malmstrom K, Ang J, Fricke JR, Shingo S, Reicin A (2005) The analgesic effect of etoricoxib relative to that of two opioid-acetaminophen analgesics: a randomized, controlled single-dose study in acute dental impaction pain. Curr Med Res Opin 21:141–149

    PubMed  CAS  Google Scholar 

  86. Chang DJ, Desjardins PJ, King TR, Erb T, Geba GP (2004) The analgesic efficacy of etoricoxib compared with oxycodone/acetaminophen in an acute postoperative pain model: a randomized, double-blind clinical trial. Anesth Analg 99:807–815

    PubMed  CAS  Google Scholar 

  87. Malmstrom K, Kotey P, Coughlin H, Desjardins PJ (2004) A randomized, double-blind, parallel-group study comparing the analgesic effect of etoricoxib to placebo, naproxen sodium, and acetaminophen with codeine using the dental impaction pain model. Clin J Pain 20:147–155

    PubMed  Google Scholar 

  88. Rasmussen GL, Malmstrom K, Bourne MH, Jove M, Rhondeau SM, Kotey P, Ang J, Aversano M, Reicin AS, Etoricoxib Postorthopedic Study Group (2005) Etoricoxib provides analgesic efficacy to patients after knee or hip replacement surgery: a randomized, double-blind, placebo-controlled study. Anesth Analg 101:1104–1111

    PubMed  CAS  Google Scholar 

  89. Malmstrom K, Kotey P, Cichanowitz N, Daniels S, Desjardins PJ (2003) Analgesic efficacy of etoricoxib in primary dysmenorrhea: results of a randomized, controlled trial. Gynecol Obstet Invest 56:65–69

    PubMed  CAS  Google Scholar 

  90. Birbara CA, Puopolo AD, Munoz DR, Sheldon EA, Mangione A, Bohidar NR, Geba GP, Etoricoxib Protocol 042 Study Group (2003) Treatment of chronic low back pain with etoricoxib, a new cyclo-oxygenase-2 selective inhibitor: improvement in pain and disability-a randomized, placebo-controlled, 3-month trial. J Pain 4:307–315

    PubMed  CAS  Google Scholar 

  91. Pallay RM, Seger W, Adler JL, Ettlinger RE, Quaidoo EA, Lipetz R, O’Brien K, Mucciola L, Skalky CS, Petruschke RA, Bohidar NR, Geba GP (2004) Etoricoxib reduced pain and disability and improved quality of life in patients with chronic low back pain: a 3 month, randomized, controlled trial. Scand J Rheumatol 33:257–66

    PubMed  CAS  Google Scholar 

  92. Zerbini C, Ozturk ZE, Grifka J, Maini M, Nilganuwong S, Morales R, Hupli M, Shivaprakash M, Giezek H, The Etoricoxib CLBP Study Group (2005) Efficacy of etoricoxib 60 mg/day and diclofenac 150 mg/day in reduction of pain and disability in patients with chronic low back pain: results of a 4-week, multinational, randomized, double-blind study. Curr Med Res Opin 21:2037–2049

    PubMed  CAS  Google Scholar 

  93. Chan VW, Clark AJ, Davis JC, Wolf RS, Kellstein D, Jayawardene S (2005) The post-operative analgesic efficacy and tolerability of lumiracoxib compared with placebo and naproxen after total knee or hip arthroplasty. Acta Anaesthesiol Scand 49:1491–1500

    PubMed  CAS  Google Scholar 

  94. Zelenakas K, Fricke JR, Jayawardene S, Kellstein D (2004) Analgesic efficacy of single oral doses of lumiracoxib and ibuprofen in patients with postoperative dental pain. Int J Clin Pract 58:251–256

    PubMed  CAS  Google Scholar 

  95. Kellstein D, Ott D, Jayawardene S, Fricke J (2004) Analgesic efficacy of a single dose of lumiracoxib compared with rofecoxib, celecoxib and placebo in the treatment of post-operative dental pain. Int J Clin Pract 58:244–250

    PubMed  CAS  Google Scholar 

  96. Bitner M, Kattenhorn J, Hatfield C, Gao J, Kellstein D (2004) Efficacy and tolerability of lumiracoxib in the treatment of primary dysmenorrhoea. Int J Clin Pract 58:340–345

    PubMed  CAS  Google Scholar 

  97. Zhao SZ, McMillen JI, Markenson JA, Dedhiya SD, Zhao WW, Osterhaus JT, Yu SS (1999) Evaluation of the functional status aspects of health-related quality of life of patients with osteoarthritis treated with celecoxib. Pharmacotherapy 19:1269–1278

    PubMed  CAS  Google Scholar 

  98. Bensen WG, Fiechtner JJ, McMillen JI, Zhao WW, Yu SS, Woods EM, Hubbard RC, Isakson PC, Verburg KM, Geis GS (1999) Treatment of osteoarthritis with celecoxib, a cyclooxygenase-2 inhibitor: a randomized controlled trial. Mayo Clin Proc 74:1095–1105

    PubMed  CAS  Google Scholar 

  99. McKenna F, Borenstein D, Wendt H, Wallemark C, Lefkowith JB, Geis GS (2001) Celecoxib versus diclofenac in the management of osteoarthritis of the knee. Scand J Rheumatol 30:11–18

    PubMed  CAS  Google Scholar 

  100. Williams GW, Hubbard RC, Yu SS, Zhao W, Geis GS (2001) Comparison of once-daily and twice-daily administration of celecoxib for the treatment of osteoarthritis of the knee. Clin Ther 23:213–227

    PubMed  CAS  Google Scholar 

  101. Kivitz AJ, Moskowitz RW, Woods E, Hubbard RC, Verburg KM, Lefkowith JB, Geis GS (2001) Comparative efficacy and safety of celecoxib and naproxen in the treatment of osteoarthritis of the hip. J Int Med Res 29:467–479

    PubMed  CAS  Google Scholar 

  102. Tannenbaum H, Berenbaum F, Reginster JY, Zacher J, Robinson J, Poor G, Bliddal H, Uebelhart D, Adami S, Navarro F, Lee A, Moore A, Gimona A (2004) Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a 13 week, randomised, double blind study versus placebo and celecoxib. Ann Rheum Dis 63:1419–1426

    PubMed  CAS  Google Scholar 

  103. Pincus T, Koch G, Lei H, Mangal B, Sokka T, Moskowitz R, Wolfe F, Gibofsky A, Simon L, Zlotnick S, Fort JG (2004) Patient Preference for Placebo, Acetaminophen (paracetamol) or Celecoxib Efficacy Studies (PACES): two randomised, double blind, placebo controlled, crossover clinical trials in patients with knee or hip osteoarthritis. Ann Rheum Dis 63:931–939

    PubMed  CAS  Google Scholar 

  104. Detrembleur C, De Nayer J, van den Hecke A (2005) Celecoxib improves the efficiency of the locomotor mechanism in patients with knee osteoarthritis. A randomised, placebo, double-blind and cross-over trial. Osteoarthritis Cartilage 13:206–210

    PubMed  CAS  Google Scholar 

  105. Sheldon E, Beaulieu A, Paster Z, Dutta D, Yu S, Sloan VS (2005) Efficacy and tolerability of lumiracoxib in the treatment of osteoarthritis of the knee: a 13-week, randomized, double-blind comparison with celecoxib and placebo. Clin Ther 27:64–77

    PubMed  CAS  Google Scholar 

  106. Lehmann R, Brzosko M, Kopsa P, Nischik R, Kreisse A, Thurston H, Litschig S, Sloan VS (2005) Efficacy and tolerability of lumiracoxib 100 mg once daily in knee osteoarthritis: a 13-week, randomized, double-blind study vs. placebo and celecoxib. Curr Med Res Opin 21:517–526

    PubMed  CAS  Google Scholar 

  107. Fleischmann R, Sheldon E, Maldonado-Cocco J, Dutta D, Yu S, Sloan VS (2006) Lumiracoxib is effective in the treatment of osteoarthritis of the knee: a prospective randomized 13-week study versus placebo and celecoxib. Clin Rheumatol 25:42–53

    PubMed  Google Scholar 

  108. Wittenberg RH, Schell E, Krehan G, Maeumbaed R, Runge H, Schlüter P, Fashola TO, Thurston HJ, Burger KJ, Trechsel U (2006) First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215]. Arthritis Res Ther 8:R35

    PubMed  Google Scholar 

  109. Rother M, Lavins BJ, Kneer W, Lehnhardt K, Seidel EJ, Mazgareanu S (2007) Efficacy and safety of epicutaneous ketoprofen in Transfersome® (IDEA-033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial. Ann Rheum Dis 66:1178–1183

    PubMed  CAS  Google Scholar 

  110. McKenna F, Weaver A, Fiechtner JJ, Bello AE, Fort JG (2001) COX-2 specific inhibitors in the management of osteoarthritis of the knee: a placebo-controlled, randomized, double-blind study. J Clin Rheumatol 7:151–159

    PubMed  CAS  Google Scholar 

  111. Smugar SS, Schnitzer TJ, Weaver AL, Rubin BR, Polis AB, Tershakovec AM (2006) Rofecoxib 12.5 mg, rofecoxib 25 mg, and celecoxib 200 mg in the treatment of symptomatic osteoarthritis: results of two similarly designed studies. Curr Med Res Opin 22:1353–1367

    PubMed  CAS  Google Scholar 

  112. Birbara C, Ruoff G, Sheldon E, Valenzuela C, Rodgers A, Petruschke RA, Chang DJ, Tershakovec AM (2006) Efficacy and safety of rofecoxib 12.5 mg and celecoxib 200 mg in two similarly designed osteoarthritis studies. Curr Med Res Opin 22:199–210

    PubMed  CAS  Google Scholar 

  113. Singh G, Fort JG, Goldstein JL, Levy RA, Hanrahan PS, Bello AE, Andrade-Ortega L, Wallemark C, Agrawal NM, Eisen GM, Stenson WF, Triadafilopoulos G, SUCCESS-I Investigators (2006) Celecoxib versus naproxen and diclofenac in osteoarthritis patients: SUCCESS-I Study. Am J Med 119:255–266

    PubMed  CAS  Google Scholar 

  114. Hawel R, Klein G, Singer F, Mayrhofer F, Kähler ST (2003) Comparison of the efficacy and tolerability of dexibuprofen and celecoxib in the treatment of osteoarthritis of the hip. Int J Clin Pharmacol Ther 41:153–164

    PubMed  CAS  Google Scholar 

  115. Geba GP, Weaver AL, Polis AB, Dixon ME, Schnitzer TJ; Vioxx, Acetaminophen, Celecoxib Trial (VACT) Group (2002) Efficacy of rofecoxib, celecoxib, and acetaminophen in osteoarthritis of the knee: a randomized trial. JAMA 287:64–71

    PubMed  CAS  Google Scholar 

  116. Schnitzer TJ, Weaver AL, Polis AB, Petruschke RA, Geba GP, VACT-1 and VACT-2 (Protocols 106 and 150) Study Groups (2005) Efficacy of rofecoxib, celecoxib, and acetaminophen in patients with osteoarthritis of the knee. A combined analysis of the VACT studies. J Rheumatol 32:1093–1105

    PubMed  CAS  Google Scholar 

  117. Luyten FP, Geusens P, Malaise M, De Clerck L, Westhovens R, Raeman F, Vander Mijnsbrugge D, Mathy L, Hauzeur JP, De Keyser F, Van den Bosch F (2007) A prospective randomised multicentre study comparing continuous and intermittent treatment with celecoxib in patients with osteoarthritis of the knee or hip. Ann Rheum Dis 66:99–106

    PubMed  CAS  Google Scholar 

  118. Leung AT, Malmstrom K, Gallacher AE, Sarembock B, Poor G, Beaulieu A, Castro R, Sanchez M, Detora LM, Ng J (2002) Efficacy and tolerability profile of etoricoxib in patients with osteoarthritis: a randomized, double-blind, placebo and active-comparator controlled 12-week efficacy trial. Curr Med Res Opin 18:49–58

    PubMed  CAS  Google Scholar 

  119. Zacher J, Feldman D, Gerli R, Scott D, Hou SM, Uebelhart D, Rodger IW, Ozturk ZE, Etoricoxib OA study group (2003) A comparison of the therapeutic efficacy and tolerability of etoricoxib and diclofenac in patients with osteoarthritis. Curr Med Res Opin 19:725–736

    PubMed  CAS  Google Scholar 

  120. Curtis SP, Bockow B, Fisher C, Olaleye J, Compton A, Ko AT, Reicin AS (2005) Etoricoxib in the treatment of osteoarthritis over 52-weeks: a double-blind, active-comparator controlled trial [NCT00242489]. BMC Musculoskelet Disord 6:58

    PubMed  Google Scholar 

  121. Wiesenhutter CW, Boice JA, Ko A, Sheldon EA, Murphy FT, Wittmer BA, Aversano ML, Reicin AS, Protocol 071 Study Group (2005) Evaluation of the comparative efficacy of etoricoxib and ibuprofen for treatment of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. Mayo Clin Proc 80:470–479

    PubMed  CAS  Google Scholar 

  122. Bingham CO, Sebba AI, Rubin BR, Ruoff GE, Kremer J, Bird S, Smugar SS, Fitzgerald BJ, O’Brien K, Tershakovec AM (2007) Efficacy and safety of etoricoxib 30 mg and celecoxib 200 mg in the treatment of osteoarthritis in two identically designed, randomized, placebo-controlled, non-inferiority studies. Rheumatology (Oxford) 46:496–507

    CAS  Google Scholar 

  123. Reginster JY, Malmstrom K, Mehta A, Bergman G, Ko AT, Curtis SP, Reicin AS (2007) Evaluation of the efficacy and safety of etoricoxib compared with naproxen in two, 138-week randomised studies of patients with osteoarthritis. Ann Rheum Dis 66:945–951

    PubMed  CAS  Google Scholar 

  124. Schnitzer TJ, Beier J, Geusens P, Hasler P, Patel SK, Senftleber I, Gitton X, Moore A, Sloan VS, Poór G (2004) Efficacy and safety of four doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: a phase II, four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 51:549–557

    PubMed  Google Scholar 

  125. Grifka JK, Zacher J, Brown JP, Seriolo B, Lee A, Moore A, Gimona A (2004) Efficacy and tolerability of lumiracoxib versus placebo in patients with osteoarthritis of the hand. Clin Exp Rheumatol 22:589–596

    PubMed  CAS  Google Scholar 

  126. Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC, Isakson PC, Verburg KM, Yu SS, Zhao WW, Geis GS (1999) Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. JAMA 282:1921–1928

    PubMed  CAS  Google Scholar 

  127. Shi W, Wang YM, Li LS, Yan M, Li D, Chen NN, Chen BY (2004) Safety and efficacy of oral nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a six-month randomised study. Clin Drug Investig 24:89–101

    PubMed  CAS  Google Scholar 

  128. Emery P, Zeidler H, Kvien TK, Guslandi M, Naudin R, Stead H, Verburg KM, Isakson PC, Hubbard RC, Geis GS (1999) Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 354:2106–2111

    PubMed  CAS  Google Scholar 

  129. Matsumoto AK, Melian A, Mandel DR, McIlwain HH, Borenstein D, Zhao PL, Lines CR, Gertz BJ, Curtis S, Etoricoxib Rheumatoid Arthritis Study Group (2002) A randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis. J Rheumatol 29:1623–1630

    PubMed  CAS  Google Scholar 

  130. Collantes E, Curtis SP, Lee KW, Casas N, McCarthy T, Melian A, Zhao PL, Rodgers DB, McCormick CL, Lee M, Lines CR, Gertz BJ, Etoricoxib Rheumatoid Arthritis Study Group (2002) A multinational randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis [ISRCTN25142273]. BMC Fam Pract 3:10

    PubMed  Google Scholar 

  131. Geusens P, Alten R, Rovensky J, Sloan VS, Krammer G, Kralidis G, Richardson P (2004) Efficacy, safety and tolerability of lumiracoxib in patients with rheumatoid arthritis. Int J Clin Pract 58:1033–1041

    PubMed  CAS  Google Scholar 

  132. Guo H, Tatsuguchi A, Shinji S, Fujimori S, Tanaka S, Gudis K, Sugisaki Y, Furukawa K, Tajiri T, Fukuda Y, Kishida T, Sakamoto C (2006) Cyclooxygenase-2 expression correlates with membrane-type-1 matrix metalloproteinase expression in colorectal cancer tissue. Dis Colon Rectum 49:1184–1192

    PubMed  Google Scholar 

  133. Joo YE, Chung IJ, Park YK, Koh YS, Lee JH, Park CH, Lee WS, Kim HS, Choi SK, Rew JS, Park CS, Kim SJ (2006) Expression of cyclooxygenase-2, p53 and Ki-67 in gastric cancer. J Korean Med Sci 21(5):871–876

    PubMed  CAS  Google Scholar 

  134. Anai S, Tanaka M, Shiverick KT, Kim W, Takada S, Boehlein S, Goodison S, Mizokami A, Rosser CJ (2007) Increased expression of cyclooxygenase-2 correlates with resistance to radiation in human prostate adenocarcinoma cells. J Urol 177:1913–1917

    PubMed  CAS  Google Scholar 

  135. Liu YS, Yu CH, Li L, Zhang BF, Fang J, Zhou Q, Hu Y, Li YM, Jun Gao H (2007) Expression of p53, p16 and cyclooxygenase-2 in esophageal cancer with tissue microarray. J Dig Dis 8:133–138

    PubMed  Google Scholar 

  136. Cui X, Zhang L, Luo J, Rajasekaran A, Hazra S, Cacalano N, Dubinett SM (2007) Unphosphorylated STAT6 contributes to constitutive cyclooxygenase-2 expression in human non-small cell lung cancer. Oncogene 26:4253–4260

    PubMed  CAS  Google Scholar 

  137. Mohammad AM, Abdel HA, Abdel W, Ahmed AM, Wael T, Eiman G (2006) Expression of cyclooxygenase-2 and 12-lipoxygenase in human breast cancer and their relationship with HER-2/neu and hormonal receptors: impact on prognosis and therapy. Indian J Cancer 43:163–168

    Article  PubMed  CAS  Google Scholar 

  138. Juuti A, Louhimo J, Nordling S, Ristimäki A, Haglund C (2006) Cyclooxygenase-2 expression correlates with poor prognosis in pancreatic cancer. J Clin Pathol 59:382–386

    PubMed  CAS  Google Scholar 

  139. Raspollini MR, Amunni G, Villanucci A, Boddi V, Taddei GL (2005) Increased cyclooxygenase-2 (COX-2) and P-glycoprotein-170 (MDR1) expression is associated with chemotherapy resistance and poor prognosis. Analysis in ovarian carcinoma patients with low and high survival. Int J Gynecol Cancer 15:255–260

    PubMed  CAS  Google Scholar 

  140. Steinbach G, Lynch PM, Phillips RK, Wallace MH, Hawk E, Gordon GB, Wakabayashi N, Saunders B, Shen Y, Fujimura T, Su LK, Levin B (2000) The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med 342:1946–1952

    PubMed  CAS  Google Scholar 

  141. Phillips RK, Wallace MH, Lynch PM, Hawk E, Gordon GB, Saunders BP, Wakabayashi N, Shen Y, Zimmerman S, Godio L, Rodrigues-Bigas M, Su LK, Sherman J, Kelloff G, Levin B, Steinbach G, FAP Study Group (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50:857–860

    PubMed  CAS  Google Scholar 

  142. Bertagnolli MM, Eagle CJ, Zauber AG, Redston M, Solomon SD, Kim K, Tang J, Rosenstein RB, Wittes J, Corle D, Hess TM, Woloj GM, Boisserie F, Anderson WF, Viner JL, Bagheri D, Burn J, Chung DC, Dewar T, Foley TR, Hoffman N, Macrae F, Pruitt RE, Saltzman JR, Salzberg B, Sylwestrowicz T, Gordon GB, Hawk ET, APC Study Investigators (2006) Celecoxib for the prevention of sporadic colorectal adenomas. N Engl J Med 355:873–884

    PubMed  CAS  Google Scholar 

  143. Arber N, Eagle CJ, Spicak J, Rácz I, Dite P, Hajer J, Zavoral M, Lechuga MJ, Gerletti P, Tang J, Rosenstein RB, Macdonald K, Bhadra P, Fowler R, Wittes J, Zauber AG, Solomon SD, Levin B, PreSAP Trial Investigators (2006) Celecoxib for the prevention of colorectal adenomatous polyps. N Engl J Med 355:885–895

    PubMed  CAS  Google Scholar 

  144. Rostom A, Dubé C, Lewin G, Tsertsvadze A, Barrowman N, Code C, Sampson M, Moher D, U.S. Preventive Services Task Force (2007) Nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors for primary prevention of colorectal cancer: a systematic review prepared for the U.S. Preventive Services Task Force. Ann Intern Med 146:376–389

    PubMed  Google Scholar 

  145. Harris RE, Beebe-Donk J, Alshafie GA (2007) Reduced risk of human lung cancer by selective cyclooxygenase 2 (COX-2) blockade: results of a case control study. Int J Biol Sci 3:328–334

    PubMed  CAS  Google Scholar 

  146. Harris RE, Beebe-Donk J, Alshafie GA (2006) Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer 6:27

    PubMed  Google Scholar 

  147. Jimeno A, Amador ML, Kulesza P, Wang X, Rubio-Viqueira B, Zhang X, Chan A, Wheelhouse J, Kuramochi H, Tanaka K, Danenberg K, Messersmith WA, Almuete V, Hruban RH, Maitra A, Yeo CJ, Hidalgo M (2006) Assessment of celecoxib pharmacodynamics in pancreatic cancer. Mol Cancer Ther 5:3240–3247

    PubMed  CAS  Google Scholar 

  148. Smith MR, Manola J, Kaufman DS, Oh WK, Bubley GJ, Kantoff PW (2006) Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy. J Clin Oncol 24:2723–2738

    PubMed  CAS  Google Scholar 

  149. Liao Z, Mason KA, Milas L (2007) Cyclo-oxygenase-2 and its inhibition in cancer: is there a role? Drugs 67:821–845

    PubMed  CAS  Google Scholar 

  150. Rubin BR, Burton R, Navarra S, Antigua J, Londoño J, Pryhuber KG, Lund M, Chen E, Najarian DK, Petruschke RA, Ozturk ZE, Geba GP (2004) Efficacy and safety profile of treatment with etoricoxib 120 mg once daily compared with indomethacin 50 mg three times daily in acute gout: a randomized controlled trial. Arthritis Rheum 50:598–606

    PubMed  CAS  Google Scholar 

  151. Schumacher HR, Boice JA, Daikh DI, Mukhopadhyay S, Malmstrom K, Ng J, Tate GA, Molina J (2002) Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis. BMJ 324:1488–1492

    PubMed  CAS  Google Scholar 

  152. Navarra S, Rubin BR, Yu Q, Smugar SS, Tershakovec AM (2007) Association of baseline disease and patient characteristics with response to etoricoxib and indomethacin for acute gout. Curr Med Res Opin 23:1685–1691

    PubMed  CAS  Google Scholar 

  153. Willburger RE, Mysler E, Derbot J, Jung T, Thurston H, Kreiss A, Litschig S, Krammer G, Tate GA (2007) Lumiracoxib 400 mg once daily is comparable to indomethacin 50 mg three times daily for the treatment of acute flares of gout. Rheumatology (Oxford) 46:1126–1132

    CAS  Google Scholar 

  154. Barkhuizen A, Steinfeld S, Robbins J, West C, Coombs J, Zwillich S (2006) Celecoxib is efficacious and well tolerated in treating signs and symptoms of ankylosing spondylitis. J Rheumatol 33:1805–1812

    PubMed  Google Scholar 

  155. Sieper J, Klopsch T, Richter M, Kapelle A, Rudwaleit M, Schwank S, Regourd E, May M (2007) Comparison of 2 different dosages of celecoxib with diclofenac for the treatment if active ankylosing spondylitis: results of a 12-week randomised double-blind controlled study. Ann Rheum Dis Jul 6; [Epub ahead of print]. DOI 10.1136/ard.2007.075309

  156. van der Heijde D, Baraf HS, Ramos-Remus C, Calin A, Weaver AL, Schiff M, James M, Markind JE, Reicin AS, Melian A, Dougados M (2005) Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. Arthritis Rheum 52:1205–1215

    PubMed  CAS  Google Scholar 

  157. Gossec L, van der Heijde D, Melian A, Krupa DA, James MK, Cavanaugh PF, Reicin AS, Dougados M (2005) Efficacy of cyclo-oxygenase-2 inhibition by etoricoxib and naproxen on the axial manifestations of ankylosing spondylitis in the presence of peripheral arthritis. Ann Rheum Dis 64:1563–1567

    PubMed  CAS  Google Scholar 

  158. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, Day R, Ferraz MB, Hawkey CJ, Hochberg MC, Kvien TK, Schnitzer TJ, VIGOR Study Group (2000). Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343:1520–1528, 2 p following 1528

    PubMed  CAS  Google Scholar 

  159. Silverstein FE, Faich G, Goldstein JL, Simon LS, Pincus T, Whelton A, Makuch R, Eisen G, Agrawal NM, Stenson WF, Burr AM, Zhao WW, Kent JD, Lefkowith JB, Verburg KM, Geis GS (2000) Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial. Celecoxib long-term arthritis safety study. JAMA 284:1247–1255

    PubMed  CAS  Google Scholar 

  160. Food and Drug Administration (2000) Celebrex capsules (celecoxib): medical officer review. http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b1_03_med.pdf (Cited 16 July 2007)

  161. Baraf HS, Fuentealba C, Greenwald M, Brzezicki J, O’Brien K, Soffer B, Polis A, Bird S, Kaur A, Curtis SP, EDGE Study Group (2007) Gastrointestinal side effects of etoricoxib in patients with osteoarthritis: results of the Etoricoxib Versus Diclofenac Sodium Gastrointestinal Tolerability and Effectiveness (EDGE) trial. J Rheumatol 34:408–420

    PubMed  CAS  Google Scholar 

  162. Laine L, Curtis SP, Cryer B, Kaur A, Cannon CP, MEDAL Steering Committee (2007) Assessment of upper gastrointestinal safety of etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 369:465–473

    PubMed  CAS  Google Scholar 

  163. Drenth JP, Verheugt FW (2007) Do COX-2 inhibitors give enough gastrointestinal protection? Lancet 369:439–440

    PubMed  Google Scholar 

  164. Psaty BM, Weiss NS (2007) NSAID trials and the choice of comparators-questions of public health importance. N Engl J Med 356:328–330

    PubMed  CAS  Google Scholar 

  165. Schnitzer TJ, Burmester GR, Mysler E, Hochberg MC, Doherty M, Ehrsam E, Gitton X, Krammer G, Mellein B, Matchaba P, Gimona A, Hawkey CJ, TARGET Study Group (2004) Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial. Lancet 364:665–674

    PubMed  CAS  Google Scholar 

  166. Ramey DR, Watson DJ, Yu C, Bolognese JA, Curtis SP, Reicin AS (2005) The incidence of upper gastrointestinal adverse events in clinical trials of etoricoxib vs. non-selective NSAIDs: an updated combined analysis. Curr Med Res Opin 21:715–722

    PubMed  CAS  Google Scholar 

  167. Rostom A, Muir K, Dubé C, Jolicoeur E, Boucher M, Joyce J, Tugwell P, Wells GW (2007) Gastrointestinal safety of cyclooxygenase-2 inhibitors: a cochrane collaboration systematic review. Clin Gastroenterol Hepatol 5:818–828

    PubMed  Google Scholar 

  168. García Rodríguez LA, Barreales Tolosa L (2007) Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population. Gastroenterology 132:498–506

    PubMed  Google Scholar 

  169. Laine L, Smith R, Min K, Chen C, Dubois RW (2006) Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 24:751–767

    PubMed  CAS  Google Scholar 

  170. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Zlotnick S, Fort JG, on behalf of the investigators (2005) Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol 3:133–141

    Google Scholar 

  171. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Aisenberg J, Bhadra P, Berger MF (2007) Small bowel mucosal injury is reduced in healthy subjects treated with celecoxib compared with ibuprofen plus omeprazole, as assessed by video capsule endoscopy. Aliment Pharmacol Ther 25:1211–1222

    Article  PubMed  CAS  Google Scholar 

  172. Chan FK, Hung LC, Suen BY, Wong VW, Hui AJ, Wu JC, Leung WK, Lee YT, To KF, Chung SC, Sung JJ (2004) Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 127:1038–1043

    PubMed  CAS  Google Scholar 

  173. Lai KC, Chu KM, Hui WM, Wong BC, Hu WH, Wong WM, Chan AO, Wong J, Lam SK (2005) Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications. Am J Med 118:1271–1278

    PubMed  CAS  Google Scholar 

  174. Chan FK, Wong VW, Suen BY, Wu JC, Ching JY, Hung LC, Hui AJ, Leung VK, Lee VW, Lai LH, Wong GL, Chow DK, To KF, Leung WK, Chiu PW, Lee YT, Lau JY, Chan HL, Ng EK, Sung JJ (2007) Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial. Lancet 369:1621–1626

    PubMed  CAS  Google Scholar 

  175. Rahme E, Barkun AN, Toubouti Y, Scalera A, Rochon S, Lelorier J (2007) Do proton-pump inhibitors confer additional gastrointestinal protection in patients given celecoxib? Arthritis Rheum 57:748–755

    PubMed  CAS  Google Scholar 

  176. Cryer B (2006) A COX-2-specific inhibitor plus a proton-pump inhibitor: is this a reasonable approach to reduction in NSAIDs’ GI toxicity? Am J Gastroenterol 101:711–713

    PubMed  CAS  Google Scholar 

  177. Scheiman JM, Yeomans ND, Talley NJ, Vakil N, Chan FK, Tulassay Z, Rainoldi JL, Szczepanski L, Ung KA, Kleczkowski D, Ahlbom H, Naesdal J, Hawkey C (2006) Prevention of ulcers by esomeprazole in at-risk patients using non-selective NSAIDs and COX-2 inhibitors. Am J Gastroenterol 101:701–710

    PubMed  CAS  Google Scholar 

  178. Spiegel BM, Farid M, Dulai GS, Gralnek IM, Kanwal F (2006) Comparing rates of dyspepsia with coxibs vs NSAID+PPI: a meta-analysis. Am J Med 119(448):e27–e36

    PubMed  Google Scholar 

  179. Bresalier RS, Sandler RS, Quan H, Bolognese JA, Oxenius B, Horgan K, Lines C, Riddell R, Morton D, Lanas A, Konstam MA, Baron JA, Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators (2005) Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 352:1092–1102

    PubMed  CAS  Google Scholar 

  180. Ott E, Nussmeier NA, Duke PC, Feneck RO, Alston RP, Snabes MC, Hubbard RC, Hsu PH, Saidman LJ, Mangano DT, Multicenter Study of Perioperative Ischemia (McSPI) Research Group, Ischemia Research and Education Foundation (IREF) Investigators (2003) Efficacy and safety of the cyclooxygenase 2 inhibitors parecoxib and valdecoxib in patients undergoing coronary artery bypass surgery. J Thorac Cardiovasc Surg 125:1481–1492

    Google Scholar 

  181. Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, Boyce SW, Verburg KM (2005) Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med 352:1081–1091

    PubMed  CAS  Google Scholar 

  182. TMT Medical (2007) TMT review: cardiovascular safety of celebrex. http://www.fda.gov/ohrms/dockets/dockets/04n0559/04N-0559_emc-000002-01.pdf Cited 16 July 2007

  183. Solomon SD, Pfeffer MA, McMurray JJ, Fowler R, Finn P, Levin B, Eagle C, Hawk E, Lechuga M, Zauber AG, Bertagnolli MM, Arber N, Wittes J, APC and PreSAP Trial Investigators (2006) Effect of celecoxib on cardiovascular events and blood pressure in two trials for the prevention of colorectal adenomas. Circulation 114:1028–1035

    PubMed  CAS  Google Scholar 

  184. Sowers JR, White WB, Pitt B, Whelton A, Simon LS, Winer N, Kivitz A, van Ingen H, Brabant T, Fort JG, Celecoxib Rofecoxib Efficacy and Safety in Comorbidities Evaluation Trial (CRESCENT) Investigators (2005) The effects of cyclooxygenase-2 inhibitors and nonsteroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med 165:161–168

    PubMed  CAS  Google Scholar 

  185. Schiffenbauer J (2005) Analysis of cardiovascular thromboembolic events with etoricoxib. http://www.fda.gov/ohrms/dockets/ac/05/slides/2005–4090S2_04_FDA-Schiffenbauer_files/slide0017.htm Cited 15 July 2007

  186. Cannon CP, Curtis SP, FitzGerald GA, Krum H, Kaur A, Bolognese JA, Reicin AS, Bombardier C, Weinblatt ME, van der Heijde D, Erdmann E, Laine L, MEDAL Steering Committee (2006) Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison. Lancet 368(9549):1771–1781

    PubMed  CAS  Google Scholar 

  187. McGettigan P, Henry D (2006) Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 296:1633–1644

    PubMed  CAS  Google Scholar 

  188. Farkouh ME, Kirshner H, Harrington RA, Ruland S, Verheugt FW, Schnitzer TJ, Burmester GR, Mysler E, Hochberg MC, Doherty M, Ehrsam E, Gitton X, Krammer G, Mellein B, Gimona A, Matchaba P, Hawkey CJ, Chesebro JH, TARGET Study Group (2004) Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial. Lancet 364:675–684

    PubMed  CAS  Google Scholar 

  189. Farkouh ME, Greenberg JD, Jeger RV, Ramanathan K, Verheugt FW, Chesebro JH, Kirshner H, Hochman JS, Lay CL, Ruland S, Mellein B, Matchaba PT, Fuster V, Abramson SB (2007) Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis 66:764–770

    PubMed  CAS  Google Scholar 

  190. Andersohn F, Suissa S, Garbe E (2006) Use of first- and second-generation cyclooxygenase-2-selective nonsteroidal antiinflammatory drugs and risk of acute myocardial infarction. Circulation 113:1950–1957

    PubMed  CAS  Google Scholar 

  191. Caldwell B, Aldington S, Weatherall M, Shirtcliffe P, Beasley R (2006) Risk of cardiovascular events and celecoxib: a systematic review and meta-analysis. J R Soc Med 99:132–140

    PubMed  CAS  Google Scholar 

  192. Chen LC, Ashcroft DM (2007) Risk of myocardial infarction associated with selective COX-2 inhibitors: meta-analysis of randomised controlled trials. Pharmacoepidemiol Drug Saf 16:762–772

    PubMed  CAS  Google Scholar 

  193. Brophy JM, Lévesque LE, Zhang B (2007) The coronary risk of cyclo-oxygenase-2 inhibitors in patients with a previous myocardial infarction. Heart 93:189–194

    PubMed  CAS  Google Scholar 

  194. Gislason GH, Jacobsen S, Rasmussen JN, Rasmussen S, Buch P, Friberg J, Schramm TK, Abildstrom SZ, Køber L, Madsen M, Torp-Pedersen C (2006) Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction. Circulation 113:2906–2913

    PubMed  CAS  Google Scholar 

  195. Helin-Salmivaara A, Virtanen A, Vesalainen R, Grönroos JM, Klaukka T, Idänpään-Heikkilä JE, Huupponen R (2006) NSAID use and the risk of hospitalization for first myocardial infarction in the general population: a nationwide case-control study from Finland. Eur Heart J 27:1657–1663

    PubMed  Google Scholar 

  196. Johnsen SP, Larsson H, Tarone RE, McLaughlin JK, Nørgård B, Friis S, Sørensen HT (2005) Risk of hospitalization for myocardial infarction among users of rofecoxib, celecoxib, and other NSAIDs: a population-based case-control study. Arch Intern Med 165:978–984

    PubMed  CAS  Google Scholar 

  197. Kearney PM, Baigent C, Godwin J, Halls H, Emberson JR, Patrono C (2006) Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomized trials. BMJ 332:1302–1308

    PubMed  CAS  Google Scholar 

  198. Rahme E, Watson DJ, Kong SX, Toubouti Y, LeLorier J (2007) Association between nonnaproxen NSAIDs, COX-2 inhibitors and hospitalization for acute myocardial infarction among the elderly: a retrospective cohort study. Pharmacoepidemiol Drug Saf 16:493–503

    PubMed  CAS  Google Scholar 

  199. Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, Shoor S, Ray WA (2005) Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 365:475–481

    PubMed  CAS  Google Scholar 

  200. White WB, West CR, Borer JS, Gorelick PB, Lavange L, Pan SX, Weiner E, Verburg KM (2007) Risk of cardiovascular events in patients receiving celecoxib: a meta-analysis of randomized clinical trials. Am J Cardiol 99:91–98

    PubMed  CAS  Google Scholar 

  201. Curtis SP, Ko AT, Bolognese JA, Cavanaugh PF, Reicin AS (2006) Pooled analysis of thrombotic cardiovascular events in clinical trials of the COX-2 selective inhibitor etoricoxib. Curr Med Res Opin 22:2365–2374

    PubMed  CAS  Google Scholar 

  202. Matchaba P, Gitton X, Krammer G, Ehrsam E, Sloan VS, Olson M, Mellein B, Hoexter G, Orloff J, Garaud JJ (2005) Cardiovascular safety of lumiracoxib: a meta-analysis of all randomized controlled trials > or = 1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis. Clin Ther 27:1196–1214

    PubMed  CAS  Google Scholar 

  203. Spalding WM, Reeves MJ, Whelton A (2007) Thromboembolic cardiovascular risk among arthritis patients using cyclooxygenase-2-selective inhibitor or nonselective cyclooxygenase inhibitor nonsteroidal anti-inflammatory drugs. Am J Ther 14:3–12

    PubMed  Google Scholar 

  204. Zhang J, Ding EL, Song Y (2006) Adverse effects of cyclooxygenase 2 inhibitors on renal and arrhythmia events: meta-analysis of randomized trials. JAMA 296:1619–1632

    PubMed  CAS  Google Scholar 

  205. Brater DC, Harris C, Redfern JS, Gertz BJ (2001) Renal effects of COX-2-selective inhibitors. Am J Nephrol 21:1–15

    PubMed  CAS  Google Scholar 

  206. Schwartz JI, Vandormael K, Malice MP, Kalyani RN, Lasseter KC, Holmes GB, Gertz BJ, Gottesdiener KM, Laurenzi M, Redfern KJ, Brune K (2002) Comparison of rofecoxib, celecoxib, and naproxen on renal function in elderly subjects receiving a normal-salt diet. Clin Pharmacol Ther 72:50–61

    PubMed  CAS  Google Scholar 

  207. Kahvecioglu S, Dilek K, Akdag I, Gullulu M, Demircan C, Ersoy A, Yurtkuran M (2006) Effect of indomethacin and selective cyclooxygenase-2 inhibitors on proteinuria and renal function in patients with AA type renal amyloidosis. Nephrology (Carlton) 11:232–237

    CAS  Google Scholar 

  208. Curtis SP, Ng J, Yu Q, Shingo S, Bergman G, McCormick CL, Reicin AS (2004) Renal effects of etoricoxib and comparator nonsteroidal anti-inflammatory drugs in controlled clinical trials. Clin Ther 26:70–83

    PubMed  CAS  Google Scholar 

  209. Wolfe F, Zhao S, Pettitt D (2004) Blood pressure destabilization and edema among 8538 users of celecoxib, rofecoxib, and nonselective nonsteroidal antiinflammatory drugs (NSAID) and nonusers of NSAID receiving ordinary clinical care. J Rheumatol 31:1143–1151

    PubMed  CAS  Google Scholar 

  210. Dilger K, Herrlinger C, Peters J, Seyberth HW, Schweer H, Klotz U (2002) Effects of celecoxib and diclofenac on blood pressure, renal function, and vasoactive prostanoids in young and elderly subjects. J Clin Pharmacol 42:985–994

    PubMed  CAS  Google Scholar 

  211. Goldenberg MM (1999) Celecoxib, a selective cyclooxygenase-2 inhibitor for the treatment of rheumatoid arthritis and osteoarthritis. Clin Ther 21:1497–1513, discussion 1427–1428

    PubMed  CAS  Google Scholar 

  212. Tsoukas C, Eyster ME, Shingo S, Mukhopadhyay S, Giallella KM, Curtis SP, Reicin AS, Melian A (2006) Evaluation of the efficacy and safety of etoricoxib in the treatment of hemophilic arthropathy. Blood 107:1785–1790

    PubMed  CAS  Google Scholar 

  213. Yazici AC, Baz K, Ikizoglu G, Kokturk A, Uzumlu H, Tataroglu C (2004) Celecoxib-induced photoallergic drug eruption. Int J Dermatol 43:459–461

    PubMed  Google Scholar 

  214. Marquès S, Milpied B, Foulc P, Barbarot S, Cassagnau E, Stalder JF (2003) Severe cutaneous drug reactions to celecoxib (Celebrex). Ann Dermatol Venereol 130:1051–1055

    PubMed  Google Scholar 

  215. Schmutz JL, Barbaud A, Trechot P (2004) Toxic epidermal necrolysis and celecoxib (Celebrex). Ann Dermatol Venereol 131:107

    PubMed  Google Scholar 

  216. Fontaine C, Bousquet PJ, Demoly P (2005) Anaphylactic shock caused by a selective allergy to celecoxib, with no allergy to rofecoxib or sulfamethoxazole. J Allergy Clin Immunol 115:633–634

    PubMed  CAS  Google Scholar 

  217. Liccardi G, Cazzola M, De Giglio C, Manfredi D, Piscitelli E, D’Amato M, D’Amato G (2005) Safety of celecoxib in patients with adverse skin reactions to acetaminophen (paracetamol) and other non-steroidal anti-inflammatory drugs. J Investig Allergol Clin Immunol 15:249–253

    PubMed  CAS  Google Scholar 

  218. Viola M, Quaratino D, Gaeta F, Caruso C, Valluzzi R, Romano A (2007) Etoricoxib tolerability in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs. Int Arch Allergy Immunol 143:103–108

    PubMed  Google Scholar 

  219. Novartis News (2007) Prexige® receives “not approvable” letter in the US despite being one of the most studied COX-2 inhibitors.

  220. Kuehn BM (2005) FDA panel: keep COX-2 drugs on market: black box for COX-2 labels, caution urged for all NSAIDs. JAMA 293:1571–1572

    PubMed  CAS  Google Scholar 

  221. Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee (2005) Minutes from Joint Meeting of the Arthritis Advisory Committee and the Drug Safety and Risk Management Advisory Committee, February 16–18, 2005. http://www.fda.gov/ohrms/dockets/ac/05/minutes/2005–4090M1_Final.pdf Cited 26 July 2007

  222. Klotz U (2005) Reassessment of the benefit/risk-ratio of selective COX-2-inhibitors. Swiss Med Wkly 135:166–168

    PubMed  Google Scholar 

  223. Henry D, McGettigan P (2007) Selective COX-2 inhibitors: a promise unfulfilled? Gastroenterology 132:790–794

    PubMed  CAS  Google Scholar 

  224. Fitzgerald GA (2007) COX-2 in play at the AHA and the FDA. Trends Pharmacol Sci 28:303–307

    PubMed  CAS  Google Scholar 

  225. Martínez-González J, Badimon L (2007) Mechanisms underlying the cardiovascular effects of COX-inhibition: benefits and risks. Curr Pharm Design 13:2215–2227

    Google Scholar 

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Acknowledgements

This work was supported by the Robert Bosch Foundation, Stuttgart, Germany.

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The authors declare that they have no conflicts of interest.

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  1. Shaojun Shi

    Present address: Department of Pharmacy of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China

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  1. Dr. Margarete Fischer-Bosch-Institut für Klinische Pharmakologie, Auerbachstraße 112, 70376, Stuttgart, Germany

    Shaojun Shi & Ulrich Klotz

  2. University of Tuebingen, Stuttgart, Germany

    Ulrich Klotz

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Shi, S., Klotz, U. Clinical use and pharmacological properties of selective COX-2 inhibitors. Eur J Clin Pharmacol 64, 233–252 (2008). https://doi.org/10.1007/s00228-007-0400-7

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