Dose-effect comparisons of the CINOD AZD3582 and naproxen on upper gastrointestinal tract mucosal injury in healthy subjects

Scandinavian Journal of Gastroenterology

Volumn 41, Issue 3, 2006, Pages 264-273

  Wilder Smith, Clive H ^a   Jonzon, Bror ^b,c   Fornstedt Wallin, Bodil ^d   Hedman, Ann ^b   Karlsson, Pär ^c  

^a Brain Gut Research Group   (Switzerland)

^b Experimental Medicine   (Sweden)

^c ASTRAZENECA R AND D   (Sweden)

^d PFIZER INC   (United States)

Author keywords

AZD3582; COX inhibiting nitric oxide donator (CINOD); Cyclooxygenase (COX); Gastrointestinal safety; Naproxen; Thromboxane B 2

Indexed keywords

CYCLOOXYGENASE INHIBITING NITRIC OXIDE DONOR; NAPROXEN; NITRIC OXIDE DONOR; NITRONAPROXEN; THROMBOXANE B2; UNCLASSIFIED DRUG;

ABDOMINAL PAIN; ADULT; ARTICLE; BREAST DISEASE; CLINICAL TRIAL; COMPARATIVE STUDY; CONNECTIVE TISSUE DISEASE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIGESTIVE SYSTEM INJURY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DOSE REGIMEN; DRUG EFFECT; DRUG SAFETY; DRUG TOLERABILITY; DUODENUM ULCER; EROSION; FATTY ACID BLOOD LEVEL; FEMALE; GASTROINTESTINAL MUCOSA; GASTROINTESTINAL TOXICITY; GENITAL SYSTEM DISEASE; HUMAN; INFECTION; INFESTATION; KIDNEY DISEASE; LOW DRUG DOSE; MALE; MEDIASTINUM DISEASE; MENTAL DISEASE; MUSCULOSKELETAL DISEASE; NEUROLOGIC DISEASE; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY TRACT DISEASE; SKIN DISEASE; STOMACH EROSION; STOMACH ULCER; THORAX DISEASE; UPPER GASTROINTESTINAL TRACT; URINARY TRACT DISEASE; VASCULAR DISEASE;

ADULT; CROSS-OVER STUDIES; CYCLOOXYGENASE INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; DUODENAL ULCER; ENDOSCOPY, GASTROINTESTINAL; FEMALE; HUMANS; INTESTINAL MUCOSA; MALE; NAPHTHALENES; NAPROXEN; REFERENCE VALUES; STOMACH ULCER; THROMBOXANE B2; TREATMENT OUTCOME;

EID: 33644588856     PISSN: 00365521     EISSN: 15027708     Source Type: Journal    
DOI: 10.1080/00365520510024197     Document Type: Article

References (25)

1. Moore RA. The hidden costs of arthritis treatment and the cost of new therapy: the burden of non-steroidal antiinflammatory drug gastropathy. Rheumatology 2002;41 Suppl 1:7-15.
2. Wolfe MM, Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med 1999;340:1888-99.
3. Haslock I. Clinical economics review: gastrointestinal complications of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 1998;12:127-33.
4. Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy. Am J Med 1998;105 Suppl 1B: 31S-8S.
5. Wallace JL. Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 1997;112:1000-16.
6. Hawkey CJ, Karrasch JA, Szczepanski L, Walker DG, Barkun A, Swannell AJ, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998;338:727-34.
7. Cryer B, Feldman M. Effects of nonsteroidal anti-inflammatory drugs on endogenous gastrointestinal prostaglandins and therapeutic strategies for prevention and treatment of nonsteroidal anti-inflammatory drug-induced damage. Arch Intern Med 1992;152:1145-55.
8. Cullen D, Bardhan KD, Eisner M, Kogut DG, Peacock RA, Thomson JM, et al. Primary gastroduodenal prophylaxis with omeprazole for non-steroidal anti-inflammatory drug users. Aliment Pharmacol Ther 1998;12:135-40.
9. Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R, Davis B, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. N Engl J Med 2000;343:1520-8.
10. Simon LS, Weaver AL, Graham DY, Kivitz AJ, Lipsky PE, Hubbard RC, et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis. A randomized controlled trial. J Am Med Assoc 1999;282:1921-8.
11. Lanas A. Clinical experience with cyclooxygenase-2 inhibitors. Rheumatology 2002;41 Suppl 1:16-22.
12. Meagher EA. Balancing gastroprotection and cardioprotection with selective cyclo-oxygenase-2 inhibitors. Clinical implications. Drug Safety 2003;26:913-24.
13. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. J Am Med Assoc 2001;286:954-9.
14. Wallace JL. Mechanisms of protection and healing: current knowledge and future research. Am J Med 2001;110 Suppl 1A:19S-23S.
15. Wallace JL, Reuter B, Cicala C, McKnight W, Grisham MB, Cirino G. Novel nonsteroidal anti-inflammatory drug derivatives with markedly reduced ulcerogenic properties in the rat. Gastroenterology 1994;107:173-9.
16. Sharma RK, Raud J, Hoogstraate O, Berge O, AstraZeneca LP, Wilmington DE. AZD3582, a COX-inhibiting nitric oxide donator (CINOD), reduces pain, inflammation and fever in rats. Clin Pharmacol Ther 2003;73:P54.
17. Hoogstraate J, Berge O, Ojteg G, Andersson LI. COX-inhibiting nitric oxide donator (CINOD): a new concept in the treatment of pain and inflammation. Ann Rheum Dis 2003;62 Suppl 1:THU0084.
18. Sharma RK, Ojteg G, Manninen A, Hallgren J, Hoogstraate J, AstraZeneca LP, Wilmington DE. AZD3582, a COX-inhibiting nitric oxide donator (CINOD): gastric tolerability profile in the rat. Clin Pharmacol Ther 2003;73:P53.
19. Wallace JL, Ojteg G, Andersson LI, Hoogstraate J. AZD3582 produces fewer and smaller gastric ulcers than naproxen in the rat refeeding model. Ann Rheum Dis 2003; 62 Suppl 1:AB0055.
20. Hawkey CJ, Jones JI, Atherton CT, Skelly MM, Bebb JR, Fagerholm U, et al. Gastrointestinal safety of AZD3582, a cyclooxygenase inhibiting nitric oxide donator: proof of concept study in humans. Gut 2003;52:1537-42.
21. Lanas A, Bajador E, Serrano P, Fuentes J, Carreno S, Guardia J, et al. Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 2000;343:834-9.
22. Hawkey C, O'Morain C, Murray F, McCarthy C, Tierney D, Devane J. Two comparative endoscopic evaluations of Naprelan. Am J Orthop 1996;25 Suppl 9:30-6.
23. Van Hecken A, Schwartz JI, Depre M, De Lepeleire I, Dallob A, Tanaka W, et al. Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. Clin Pharmacol 2000;40:1109-20.
24. James MW, Hawkey CJ. Assessment of non-steroidal anti-inflammatory drug (NSAID) damage in the human gastrointestinal tract. Br J Clin Pharmacol 2003;56:146-55.
25. Lohmander S, McKeith D, Svensson O, Malmenäs M, Bolin L, Kalla A, et al. A randomised, placebo-controlled, comparative trial of the gastrointestinal safety and efficacy of AZD3582 versus naproxen in osteoarthritis. Ann Rheum Dis 2005;64: 449-56.