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Mathematical model for assessing risk of gastrointestinal reactions to NSAIDs

  • Chapter
Azapropazone

Abstract

In vitro data indicate that all clinically useful non-steroidal anti-inflammatory drugs (NSAIDs) inhibit to a varying degree the activity of the enzyme cyclo-oxygenase. It has been argued that the failure of certain NSAIDs to significantly reduce gastric mucosal levels of prostaglandins (PG) in vivo may reflect pharmacokinetic differences between NSAIDs rather than tissue-specific differences in their potency as inhibitors of cyclo-oxygenase1. A corollary of such an argument is that accumulation of NSAID within gastric mucosal cells is a principal factor associated with the intervention of intracellular biochemical events and resultant gastric mucosal damage.

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References

  1. McCormack, K and Brune, K (1987). Classical absorption theory and the development of gastric mucosal damage associated with the non-steroidal anti-inflammatory drugs. Arch Toxicol, 60, 261–9

    Article  PubMed  CAS  Google Scholar 

  2. Shore, PA, Brodie, BB and Hogben, CAM (1950). The gastric secretion of drugs. A pH partition hypothesis. J Pharmacol, 119, 361–9

    Google Scholar 

  3. Hogben, CAM, Schanker, LS, Tocco, DJ and Brodie, BB (1957). Absorption of drugs from the stomach. II. The human. J Pharmacol, 120, 540–5

    CAS  Google Scholar 

  4. Hogben, CAM, Tocco, DJ, Brodie, BB and Sehanker, LS (1959). On the mechanism of intestinal absorption of drugs. J Pharmacol, 125, 275–82

    CAS  Google Scholar 

  5. Schanker, LS (1959). Absorption of drugs from the rat colon. J Pharmacol, 126, 81–8

    Google Scholar 

  6. Schanker, LS, Shore, PA, Brodie, BB and Hogbèn, CAM (1957). Absorption of drugs from the stomach. The rat. J Pharmacol, 123, 81–8

    Google Scholar 

  7. Schanker, LS, Tocco, DJ, Brodie, BB and Hogben, CAM (1958). Absorption of drugs from the rat small intestine. J Pharmacol, 123, 81–8

    CAS  Google Scholar 

  8. Martin, BK (1963). Accumulation of drug anions in gastric mucosal cells. Nature, 198, 896–7

    Article  CAS  Google Scholar 

  9. Brune, K, Schweitzer, A and Eckert, H (1977). Parietal cells of the stomach trap salicylates during absorption. Biochem Pharmacol, 26, 1735–40

    Article  PubMed  CAS  Google Scholar 

  10. Brune, K, Gubler, H and Schweitzer, A (1979). Autoradiographic methods for the evaluation of ulcerogenic effects of anti-inflammatory drugs. Pharmacol Ther, 5, 199–207

    Article  CAS  Google Scholar 

  11. Rainsford, KD and Brune, K (1978). Selective cytotoxic actions of aspirin on parietal cells: a principal factor in the early stages of aspirin-induced gastric damage. Arch Toxicol, 40, 143–50

    Article  PubMed  CAS  Google Scholar 

  12. Leonards, JR (1963). The influence of solubility on the rate of gastrointestinal absorption of aspirin. Clin Pharmacol Ther, 4, 476–81

    PubMed  CAS  Google Scholar 

  13. Brune, K and Lanze, R (1985). Pharmacokinetics of non-steroidal antiinflammatory drugs. Handbook of Inflammation, 5, 413–49

    CAS  Google Scholar 

  14. Edwards, FC and Coghill, NF (1966). Aetiological factors in chronic atrophic gastritis. Brit Med J, 2, 1409–15

    Article  PubMed  CAS  Google Scholar 

  15. Mukawa, K, Nakamura, T, Nakano, G and Magamachi, Y (1987). Histopathogenesis of intestinal metaplasia: minute lesions of intestinal metaplasia in ulcerated stomachs. J Clin Pathol, 40, 13–8

    Article  PubMed  CAS  Google Scholar 

  16. Tatsuta, M, Iishi, H and Okada, S. (1988). Dig Dis Sci, 33, 23–9

    Article  PubMed  CAS  Google Scholar 

  17. Upadhyay, R, Howatson, A, McKinlay, A, Danesh, BJZ, Sturrock, RD and Russell, RI (1988). Campylobacter pylori associated gastritis in patients with rheumatoid arthritis taking non-steroidal antiinflammatory drugs. Brit J Rheum, 27, 113–6

    Article  CAS  Google Scholar 

  18. Doube, A and Morris, A (1988). Non-steroidal anti-inflammatory drug-induced dyspepsia — is Campylobacter pyloridis implicated? Brit J Rheum, 27, 110–2

    Article  CAS  Google Scholar 

  19. Kohli, Y, Kato, T, Suzuki, K, Tada, T and Fujiki, N (1987). Incidence of atrophic gastritis with age in Japan and Canada. Jpn J Med, 26, 158–61

    Article  PubMed  CAS  Google Scholar 

  20. Tsuneoka, K, Hirakawa, T, Matsushita, K et al. (1977). The digestive tract in aging. Stomach Intest, 12, 577–90

    Google Scholar 

  21. Roberts, DM (1972). Chronic gastritis, alcohol and non-ulcer dyspepsia. Gut, 13, 768–74

    Article  PubMed  CAS  Google Scholar 

  22. Delaney, JP, Broadie, TA and Robbins, PL (1975). Pyloric reflux gastritis: the offending agent. Surgery, 6, 764–72

    Google Scholar 

  23. Strickland, RG and Mackay, IR (1973). A reappraisal of the nature and significance of chronic atrophic gastritis. Am J Dig Dis, 18, 426–40

    Article  PubMed  CAS  Google Scholar 

  24. Kekki, M, Siurala, M, Varis, K, Sipponen, P, Sistonen, P and Nevanlinna, HR (1987). Classification principles and genetics of chronic gastritis. Scand J Gastroent, 22, (Suppl. 141), 1–28

    Article  Google Scholar 

  25. Siurala, M, Isokoski, M, Varis, K and Kekki, M (1968). Prevalence of gastritis in a rural population. Scand J Gastroent, 3, 211–23

    Article  PubMed  CAS  Google Scholar 

  26. Siurala, M, Varis, K and Kekki, M (1980). New aspects on epidemiology, genetics and dynamics of chronic gastritis. Front Gastrointest Res, 6, 148–66

    PubMed  CAS  Google Scholar 

  27. Ihamaki, T, Saukkonen, M and Siurala, M (1978). Long-term observation of subjects with normal mucosa and with superficial gastritis: results of 23–27 years follow-up examinations. Scand J Gastroent, 13, 771–5

    Article  PubMed  CAS  Google Scholar 

  28. Villako, K, Kekki, M, Tamm, A and Savisaar, E (1986). Development and progression of chronic gastritis in the antrum and body mucosa: results of long-term follow-up examinations. Ann Clin Res, 18, 121–3

    PubMed  CAS  Google Scholar 

  29. Cheli, R, Simon, L, Aste, H et al (1980). Atrophie gastritis and intestinal metaplasia in asymptomatic Hungarian and Italian populations. Endoscopy, 12, 105–8

    Article  PubMed  CAS  Google Scholar 

  30. Winawer, SJ, Bejar, J, McCray, RS and Zamcheck, N (1971). Hemorrhagic gastritis. Arch Intern Med, 127, 129–31

    Article  PubMed  CAS  Google Scholar 

  31. Chapman, MA, Werther, JL and Janowitz, HD (1968). Response of the normal and pathological human gastic mucosa to an instilled acid load. Gastroenterology, 55, 344–53

    PubMed  CAS  Google Scholar 

  32. Ritchie, WP and Delaney, JP (1971). Susceptibility of experimental atrophic gastritis to ulceration. Gastroenterology, 60, 554–9

    PubMed  Google Scholar 

  33. Ritchie, WP, Butler, BA and Delaney, JP (1972). Studies on the pathogenesis of benign gastric ulcer: increased back diffusion of hydrogen ion in experimental atrophic gastritis. Ann Surg, 175, 594–600

    Article  PubMed  Google Scholar 

  34. Kivilaakso, E, Fromm, D and Silen, W (1978). Effect of the acid secretory state on intramural pH of rabbit gastric mucosa. Gastroenterology, 75, 641–8

    PubMed  CAS  Google Scholar 

  35. Fromm, D and Kolois, M (1982). Effects of sodium salicylate and acetylsalicylic acid on intramural pH and ulceration of rabbit antral mucosa. Surgery, 91, 438–47

    PubMed  CAS  Google Scholar 

  36. Brune, K, Rainsford, KD, Wagner, K and Peskar, BA (1981). Inhibition by anti-inflammatory drugs of prostaglandin production in cultured macrophages. Arch Pharmacol, 315, 269–76

    Article  CAS  Google Scholar 

  37. McCormack, K and Brune, K (1989). The amphiprotic character of azapropa-zone and its relevance to the gastric mucosa. Article in press — Arch Toxicol.

    Google Scholar 

  38. Klatt, L, and Koss, FW (1973). Pharmacokinetic studies with azapropazone dihydrate, labelled with carbon-14, in the rat. Arzneim Forsch, 23(7), 913–9

    Google Scholar 

  39. Jahn, V, Relier, J and Schatz, F (1973). Pharmacokinetic experiments with azapropazone in animals. Arzneim Forsch, 13(5), 660–6

    Google Scholar 

  40. Upadhyay, R, Duncan, A, Walker, FS and Russell, RI (1989). A new method for studying gastric arid intestinal absorption of drugs and its application to azapropazone. Eur J Clin Pharmacol (In press)

    Google Scholar 

  41. Herzfeldt, CD and Kümmel, R (1983). Dissociation constants, solubilities and dissolution rates of some selected non-steroidal anti-inflammatories. Drug Dev Ind Pharm, 9(5), 767–93

    Article  CAS  Google Scholar 

  42. Krebs, HA and Speakman, JC (1945). The effect of pH on the solubility of sulphanamides. Biochem J, 39, xlii

    Google Scholar 

  43. Verbeeck, RK, Blackburn, JL and Loewen, GR (1983). Clinical pharmacokinetics of non-steroidal anti-inflammatory drugs. Clin Pharmacokinet, 8, 297–331

    Article  PubMed  CAS  Google Scholar 

  44. Grennan, DM and Higham, C (1986). Non-steroidal anti-inflammatory drugs. In: Mol, JMH et al. (eds), Therapeutics in Rheumatology (Cambridge: Cambridge University Press)

    Google Scholar 

  45. Marsh, CC, Schuna, AA and Sundstrom, MD (1986). A review of selected investigational non-steroidal anti-inflammatory drugs of the 1980s. Pharmacotherapy, 6(1), 10–25

    PubMed  CAS  Google Scholar 

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Authors
  1. K. McCormack
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Editors and Affiliations

  1. Department of Biomedical Sciences, McMaster University Faculty of Health Sciences, 1200 Main St W, Hamilton, Ontario, L8N 3Z5, Canada

    K. D. Rainsford

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© 1989 Kluwer Academic Publishers

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McCormack, K. (1989). Mathematical model for assessing risk of gastrointestinal reactions to NSAIDs. In: Rainsford, K.D. (eds) Azapropazone. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0713-3_7

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  • DOI: https://doi.org/10.1007/978-94-009-0713-3_7

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6806-2

  • Online ISBN: 978-94-009-0713-3

  • eBook Packages: Springer Book Archive

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