Skip to main content
SpringerLink
Log in

Clinical pharmacology of mesalazine (5-aminosalicylic acid) in chronic inflammatory bowel disease

  • Chapter
Clinical Research in Gastroenterology 2

Abstract

Several new salicylate compounds have been developed in recent years as a result of intensive clinical research with sulphasalazine (SZ). Since its discovery in 1941 SZ has been used as a kind of standard drug in the treatment of chronic inflammatory bowel disease (IBD); especial benefit has been obtained in the management of ulcerative colitis patients. However, therapy with this azo-compound is often limited by dose-dependent side effects and intolerance (for review see references 1 and 2). The mode of action of SZ is still unknown but metabolic and clinical studies have raised the question of whether it is the entire molecule or a metabolite that is the therapeutic principal. In the first controlled clinical trials it was realized that 5-aminosalicylic acid, a major primary metabolite of SZ (now renamed mesalazine) represents the active therapeutic moiety 3–5. During the last few years these initial studies have been confirmed by numerous investigations and clinical experience with mesalazine has been accumulating. Nowadays this salicylate has a well-established place in the treatment of IBD, especially for such patients as are sensitive to SZ6–9.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bachrach, W.H. (1988). Sulfasalazine: I. An historical perspective. Am. J. Gastroenterol., 83, 487–96

    PubMed  CAS  Google Scholar 

  2. Peppercorn, NA. (1984). Sulfasalazine-pharmacology, clinical use, toxicity, and related new drug development. Ann. Intern. Med., 3, 377–86

    Google Scholar 

  3. Azad Khan, K.A., Piris, J. and Truelove, S.C. (1977). An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet, 2, 892–5

    Article  PubMed  CAS  Google Scholar 

  4. van Hees, PA.M., Bakker, J.H. and van Tongeren, J.H.M. (1980). Effect of sulfapyridine, 5-aminosalicylic acid, and placebo in patients with idiopathic proctitis: a study to determine the active therapeutic moiety of sulphasalazine. Gut, 21, 632–5

    Article  PubMed  Google Scholar 

  5. Klotz, U., Maier, K., Fischer, C. and Heinkel, K. (1980). Therapeutic efficacy of sulfasalazine and its metabolites in patients with ulcerative colitis and Crohn’s disease. N. Engl. J. Med., 303, 1499–502

    Article  PubMed  CAS  Google Scholar 

  6. Hawkey, CJ. (1986). Salicylates for the sulfa-sensitive patient with ulcerative colitis. Gastroenterology, 90, 1082–4

    PubMed  CAS  Google Scholar 

  7. Williams, C.N. (1987). Clinical experience with 5-aminosalicylate preparations in inflammatory bowel disease — a review. Can. J. Gastroenterol., 83, 64–7

    Google Scholar 

  8. Meyer, S. (1988). The place of oral 5-aminosalicylic acid in the therapy of ulcerative colitis. Am. J. Gastroenterol., 83, 64–7

    Google Scholar 

  9. Margolin, M.L., Krumholz, M.P., Fochios, S.E. and Korelitz, B.I. (1988). Clinical trials in ulcerative colitis: II. Historical review. Am. J. Gastroenterol., 83, 227–43

    PubMed  CAS  Google Scholar 

  10. Campieri, M., Lanfranchi, G.A., Brignola, C. et al. (1984). A double blind clinical trial to compare the effects of 4-aminosalicylic acid to 5-aminosalicylic acid in topical treatment of ulcerative colitis. Digestion, 29, 478–9

    Article  Google Scholar 

  11. Myers, B., Evans, D.N.W., Rhodes, J., Evans, B.K., Hughes, B.R., Lee, M.G., Richens, A. and Richards, D. (1987). Metabolism and urinary excretion of 5-aminosalicylic acid in healthy volunteers when given intravenously or released for absorption at different sites in the gastrointestinal tract. Gut, 196–200

    Google Scholar 

  12. Dew, M.J., Ryder, R.E.J., Evans, N., Evans, B.K. and Rhodes, J. (1983). Colonic release of 5-aminosalicylic acid from an oral preparation in active ulcerative colitis. Br. J. Clin. Pharmacol., 16, 185–7

    PubMed  CAS  Google Scholar 

  13. Rasmussen, S.N., Bondesen, S., Hvidberg, E.F., Hansen, S.H., Binder, V., Halskov, S. and Flachs, H. (1982). 5-Aminosalicylic acid in slow release preparation: bioavailability, plasma level and excretion in humans. Gastroenterology, 83, 1062–70

    PubMed  CAS  Google Scholar 

  14. Klotz, U., Maier, K.E., Fischer, C. and Bauer, K.H. (1985). A new slow-release form of 5-aminosalicylic acid for the oral treatment of inflammatory bowel disease. Biopharma-ceutical and clinical pharmacokinetic characteristics. Arzneim. Forsch., 35, 636–9

    CAS  Google Scholar 

  15. Hardy, J.G., Healey, J.N.C., Lee, S.W. and Reynolds, J.R. (1987). Gastrointestinal transit of an enteric-coated delayed-release 5-aminosalicylic acid tablet. Aliment. Pharmacol. Ther., 1, 209–16

    Article  PubMed  CAS  Google Scholar 

  16. Hardy, J.G., Healey, J.N.C. and Reynolds, J.R. (1987). Evaluation of an enteric-coated delayed release 5-aminosalicylic acid tablet in patients with inflammatory bowel disease. Aliment. Pharmacol. Ther., 1, 273–80

    Article  PubMed  Google Scholar 

  17. Klotz, U., Seyffer, R., Allgayer, H. and Maier, K.E. (1988). Pharmacokinetic properties of mesalazine (5-aminosalicylic acid). In MacDermott, R.P. (ed.) Inflammatory Bowel Disease, pp. 725–9. (Amsterdam: Elsevier Science Publisher)

    Google Scholar 

  18. Rijk, M.C.M., van Schaik, A. and van Tongeren, J.H.M. (1988). Disposition of 5-aminosalicylic acid by 5-aminosalicylic acid-delivering compounds. Scand. J. Gastroenterol., 23, 107–12

    Article  PubMed  CAS  Google Scholar 

  19. Bondesen, S., Nielsen, O.H., Schou, J.B., Jensen, P.H., Lassen, L.B., Binder, V., Krasilnikoff, P.A., Dano, P., Hansen, S.H., Rasmussen, S.N. and Hvidberg, E.F. (1986). Steady-state kinetics of 5-aminosalicylic acid and sulfapyridine during sulfasalazine prophylaxis in ulcerative colitis. Scand. J. Gastroenterol., 21, 693–700

    Article  PubMed  CAS  Google Scholar 

  20. Christensen, LA., Slot, O., Sanchez, G., Boserup, J., Rasmussen, S.N., Bondesen, S., Hansen, S.H. and Hvidberg, E.F. (1987). Release of 5-aminosalicylic acid from Pentasa during normal and accelerated intestinal transit time. Br. J. Clin. Pharmacol., 23, 365–9

    PubMed  CAS  Google Scholar 

  21. Dew, M.J., Cardwell, M., Kidwai, N.S., Evans, B.K. and Rhodes, E.J. (1983). 5-Aminosalicylic acid in serum and urine after administration by enema to patients with colitis. J. Pharm. Pharmacol., 35, 323–4

    Article  PubMed  CAS  Google Scholar 

  22. Bondesen, S., Nielsen, O.H., Jacobsen, O., Rasmussen, S.N., Hansen, S.H., Halskov, S., Binder, V. and Hvidberg, E.F. (1984). 5-Aminosalicylic acid enemas in patients with active ulcerative colitis. Scand. J. Gastroenterol., 19, 677–82

    PubMed  CAS  Google Scholar 

  23. Bondesen, S., Schou, J.B., Pedersen, V., Rafiolsada, Z., Hansen, S.H. and Hvidberg, E.F. (1988). Absorption of 5-aminosalicylic acid from colon and rectum. Br. J. Clin. Pharmacol., 25, 269–72

    PubMed  CAS  Google Scholar 

  24. Fischer, C., Maier, K., Stumpf, E., von Gaisburg, U. and Klotz, U. (1983). Disposition of 5-aminosalicylic acid, the active metabolite of sulphasalazine, in man. Eur. J. Clin. Pharmacol., 25, 511–5

    Article  PubMed  CAS  Google Scholar 

  25. Rasmussen, S.N., Binder, V., Maier, K., Bondesen, S., Fischer, C., Klotz, U., Hansen, S.H. and Hvidberg, E.F. (1983). Treatment of Crohn’s disease with peroral 5-aminosalicylic acid. Gastroenterology, 85, 1350–3

    PubMed  CAS  Google Scholar 

  26. Klotz, U. (1986). Klinische Pharmakologie von 5-Aminosalicylsäure. In Ewe, K. and Fahrländer, H. (eds.) Therapie chronisch entzündlicher Darmerkrankungen, pp. 221–7. (Stuttgart/New York: Schattauer Verlag)

    Google Scholar 

  27. Fischer, C., Maier, K. and Klotz, U. (1983). Specific measurements of 5-aminosalicylic acid and its acetylated metabolite in human bile. Br. J. Clin. Pharmacol., 15, 273–4

    PubMed  CAS  Google Scholar 

  28. Klotz, U. (1988). Pharmacokinetic properties of 5-aminosalicylic acid (mesalazine). In Goebell, H., Peskar, B.M. and Malchow, H. (eds.) Inflammatory bowel disease — basic research and clinical implications, pp. 339–47. (Lancaster: MTP Press)

    Google Scholar 

  29. Tolia, V., Massoud, N. and Klotz, U. (1989). Oral 5-aminosalicylic acid in children with chronic inflammatory bowel disease: clinical and pharmacokinetic experience. J. Pediatr. Gastroenterol., 8, 333–338

    Article  CAS  Google Scholar 

  30. Klotz, U. (1985). Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin. Pharmacofänet., 10, 285–302

    Article  CAS  Google Scholar 

  31. Fischer, C., Meese, C.O. and Klotz, U. (1984). A stable isotope method for the quantification of N-acetyl-5-aminosalicylic acid in plasma and urine. Biomed. Mass Spectrum, 11, 539–44

    Article  CAS  Google Scholar 

  32. Meese, CO., Fischer, C and Klotz, U. (1984). Is N-acetylation of 5-aminosalicylic acid reversible in man? Br. J. Clin. Pharmacol., 18, 612–5

    PubMed  CAS  Google Scholar 

  33. Allgayer, H., Kruis, W. and Paumgartner, G. (1984). Azetylatorstatusunabhängige N-Acetyltransferaseaktivität im Kolon bei Patienten mit colitis ulcerosa unter Sulfasalazin-Dauertherapie. Z. Gastroenterol., 22, 131

    Google Scholar 

  34. Layer, P., Goebell, H., Nehlsen, B. and Klotz, U. (1989). Small intestinal transit and delivery to the distal ileal lumen of oral slow release mesalazine (5-ASA) in humans. Gastroenterol., 96, A292

    Google Scholar 

  35. Shaffer, J.L., Turner, M. and Houston, J.B. (1985). Disposition of 5-aminosalicylic acid preparation in patients with inflammatory bowel disease. Br. J. Clin. Pharmacol., 20, 532P

    Google Scholar 

  36. Willoughby, C.P., Aronson, J.K., Agback, H., Boden, N.O. and Truelove, S.C. (1982). Distribution and metabolism in healthy subjects of disodium azodisalicylate, a potential therapeutic agent for ulcerative colitis. Gut, 23, 1081–7

    Article  PubMed  CAS  Google Scholar 

  37. van Hogezand, R.A., van Hees, PA.M., Zwanenburg, B., van Rossum, J.M. and van Tongeren, J.H.M. (1985). Disposition of disodium azodisalicylate in healthy subjects. Gastroenterology, 88, 17–22

    Google Scholar 

  38. Ryde, E.M. and Ahnfelt, N.O. (1988). The pharmacokinetics of olsalazine sodium in healthy volunteers after a single i.v. dose and after oral doses with and without food. Eur. J. Clin. Pharmacol., 34, 481–8

    Article  PubMed  CAS  Google Scholar 

  39. Klotz, U. and Maier, K.E. (1987). Pharmacology and pharmacokinetics of 5-aminosalicylic acid. Dig. Dis. Sci., 32, 46S–50S

    Article  PubMed  CAS  Google Scholar 

  40. Rasmussen, S.N., Lauritsen, K., Tage-Jensen, U., Nielsen, O.H., Bytzer, P., Jacobsen, O., Ladefoged, K., Vilien, M., Bincer, V., Rask-Madsen, J., Bondesen, S., Hansen, S.H. and Hvidberg, E.F. (1987). 5-Aminosalicylic acid in the treatment of Crohn’s disease. Scand. J. Gastroenterol., 22, 877–83

    Google Scholar 

  41. Schroeder, K.W., Tremaine, W.J. and Ilstrup, D.M. (1987). Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. N. Engl. J. Med., 317, 1625–9

    Article  PubMed  CAS  Google Scholar 

  42. Habal, F.M. and Greenberg, G.R. (1988). Treatment of ulcerative colitis with oral 5-aminosalicylic acid including patients with adverse reactions to sulfasalazine. Am. J. Gastroenterol., 83, 15–19

    PubMed  CAS  Google Scholar 

  43. Riley, S.A., Mani, V., Goodman, M.J., Herd, M.E., Dutt, S. and Turnberg, LA. (1983). Comparison of delayed release 5-aminosalicylic acid (mesalazine) and sulphasalazine in treatment of mild to moderate ulcerative colitis relapse. Gut, 29, 669–74

    Article  Google Scholar 

  44. van Hogezand, R.A., van Hees, PA.M., van Gorp, J.P.W.M., van Lier, H.J.J., Bakker, J.H., Wesseling, P., van Haelst, U.J.G.M. and van Tongeren, J.H.M. (1988). Double-blind comparison of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid suppositories in patients with idiopathic proctitis. Aliment. Pharmacol. Ther., 2, 33–40

    Article  PubMed  Google Scholar 

  45. Basilisco, G., Ranzi, T., Campanini, M., Piodi, L., Velio, P. and Bianchi, PA. (1987). 5-Aminosalicylic acid or sulfasalazine retention enemas in distal ulcerative colitis. Curr. Ther. Res., 42, 910–5

    Google Scholar 

  46. Sutherland, L.R., Martin, F., Greer, S., Robinson, M., Greenberger, N., Saibil, F., Martin, T., Sparr, J., Prokipchuk, E. and Borgen, L. (1987). 5-Aminosalicylic acid enemas in the treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis. Gastroenterology, 92, 1894–8

    PubMed  CAS  Google Scholar 

  47. Riley, S.A., Mani, V., Goodman, M.J., Herd, M.E., Dutt, S. and Turnberg, LA. (1988). Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis. Gastroenterology, 94, 1383–9

    PubMed  CAS  Google Scholar 

  48. Sutherland, L.R. and Martin, F. (1987). 5-Aminosalicylic acid enemas in the maintenance of remission in distal ulcerative colitis and proctitis. Can. J. Gastroenterol., 1, 3–6

    Google Scholar 

  49. Biddle, W.L., Greenberger, N.J., Swan, T., McPhee, M.S. and Miner Jr., P.B. (1988). 5-Aminosalicylic acid enemas. Effective agent in maintaining remission in left-sided ulcerative colitis. Gastroenterology, 94, 1075–9

    PubMed  CAS  Google Scholar 

  50. Burke, D.A., Manning, A.P., Williamson, J.M.S. and Axon, A.T.R. (1987). Adverse reactions to sulphasalazine and 5-amino salicylic acid in the same patient. Aliment. Pharmacol. Ther., 1, 201–8

    Article  PubMed  CAS  Google Scholar 

  51. Turunen, U., Elomaa, I., Anttila, V-J and Seppälä, K. (1987). Mesalazine tolerance in patients with inflammatory bowel disease and previous intolerance or allergy to sulphasalazine or sulphonamides. Scand. J. Gastroenterol., 22, 798–802

    Article  PubMed  CAS  Google Scholar 

  52. Winter, K., Bondesen, S., Hansen, S.H. and Hvidberg, E.F. (1987). Lack of effect of 5-aminosalicylic acid on platelet aggregation and fibrinolytic activity in vivo and in vitro. Eur. J. Clin. Pharmacol., 33, 419–22

    Article  Google Scholar 

  53. Diener, U., Tuczek, H.V., Fischer, C., Maier, K. and Klotz, U. (1984). Renal function was not impaired by treatment with 5-aminosalicylic acid in rats and man. Naunyn-Schmiedeberg’s Arch. Pharmacol., 326, 278–82

    Article  CAS  Google Scholar 

  54. Campieri, M., Brignola, C., Bazzocchi, G., Minguzzi, M.R., Gionchetti, P., Belluzzi, A., Adami, F., Basso, O., Migaldi, M.P. and Lanfranchi, G.A. (1986). Several aspects of topical treatment with 5-aminosalicylic acid enemas. In Ewe, K. and Fahrländer, H. (eds.) Therapie chronisch entzündlicher Darmerkrankungen-Fortschritte, Entwicklungen, Tendenzen pp. 237–42. (Stuttgart/New York: Schattauer)

    Google Scholar 

  55. Meyers, S., Sachar, D.B., Present, D.H. and Janowitz, H.D. (1987). Olsalazine sodium in the treatment of ulcerative colitis among patients intolerant to sulfasalazine. Gastroenterology, 93, 1255–62

    PubMed  CAS  Google Scholar 

  56. Selby, W.S., Barr, G.D., Ireland, A., Mason, C.H. and Jewell, D.P. (1985). Olsalazine in active ulcerative colitis. Br. Med. J., 291, 1373–5

    Article  CAS  Google Scholar 

  57. Sandberg-Gertzen, H., Jarnerot, G. and Kraaz, W. (1986). Azodisal sodium in the treatment of ulcerative colitis. Gastroenterology, 90, 1024–30

    PubMed  CAS  Google Scholar 

  58. Hetzel, D.J., Shearman, D.J.C., Bochner, F., Imhoff, D.M., Gibson, G.E., Fitch, R.J., Hecker, R., Labrooy, J. and Rowland, R. (1986). Azodisalicylate (olsalazine) in the treatment of active ulcerative colitis. A placebo controlled clinical trial and assessment of drug disposition. J. Gastroenterol. Hepatol., 1, 257–66

    Article  Google Scholar 

  59. Lauritsen, K., Laursen, L.S., Bukhave, K. and Rask-Madsen, J. (1988). Longterm olsalazine treatment: pharmacokinetics, tolerance and effects on local eicosanoid formation in ulcerative colitis and Crohn’s colitis. Gut, 29, 974–82

    Article  PubMed  CAS  Google Scholar 

  60. Robinson, M.G. and Dorrough, C. (1987). Azodisalicylate sodium in the treatment of ulcerative colitis. A randomized double-blind, placebo-controlled clinical trial. Am. J. Gastroenterol., 82, Abstract 124

    Google Scholar 

  61. Stenson, W.F. and Lobos, E. (1982). Sulfasalazine inhibits the synthesis of chemotactic lipids by neutrophils. J. Clin. Invest., 69, 494–7

    Article  PubMed  CAS  Google Scholar 

  62. Peskar, B.M., Dreyling, K.W., Peskar, BA, May, B. and Goebell, H. (1986). Enhanced formation of sulfidopeptide-leukotrienes in ulcerative colitis and Crohn’s disease: inhibition by sulfasalazine and 5-aminosalicylic acid. Agents Actions, 18, 381–3

    Article  PubMed  CAS  Google Scholar 

  63. Roediger, W., Schapel, G., Lawson, M., Radcliffe, B. and Nance, S. (1986). Effect of 5-aminosalicylic acid (5-ASA) and other salicylates on short-chain fat metabolism in the colonic mucosa. Biochem. Pharmacol., 35, 221–5

    Article  PubMed  CAS  Google Scholar 

  64. Miyachi, Y., Yoshioka, A., Imamura, S. and Niwa, Y. (1987). Effect of sulphasalazine and its metabolites on the generation of reactive oxygen species. Gut, 28, 190–5

    Article  PubMed  CAS  Google Scholar 

  65. Craven, PA., Pfanstiel, J., Saito, R. and de Rubertis, F.R. (1987). Actions of sulfasalazine and 5-aminosalicylic acid as reactive oxygen scavengers in the suppression of bile acid-induced increases in colonic epithelial cell loss and proliferative activity. Gastroenterology, 92, 1998–2008

    PubMed  CAS  Google Scholar 

  66. Kvietys, P.R., Smith, S.M., Grisham, M.B. and Manci, EA. (1988). 5-Aminosalicylic acid protects against ischemia/reperfusion-induced gastric bleeding in the rat. Gastroenterology, 94, 733–8

    PubMed  CAS  Google Scholar 

  67. Willoughby, C.P., Piris, J. and Truelove, S.C. (1980). The effect of topical N-acetyl-5-aminosalicylic acid in ulcerative colitis. Scand. J. Gastroenterol., 15, 715–9

    Article  PubMed  CAS  Google Scholar 

  68. Binder, V., Halskov, S., Hvidberg, E., Kristensen, E., Riis, P., Tougaard, L. and Willumsen, L. (1981). A controlled study of 5-acetylaminosalicylic acid (5-ac-ASA) as enema in ulcerative colitis. Scand. J. Gastroenterol., (Abstract), 16, 1122

    Google Scholar 

Download references

Authors
  1. U. Klotz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medical Faculty of Aachen University of Technology, Aachen, Germany

    S. Matern (Director of the Third Department of Internal Medicine) (Director of the Third Department of Internal Medicine)

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Kluwer Academic Publishers

About this chapter

Cite this chapter

Klotz, U. (1989). Clinical pharmacology of mesalazine (5-aminosalicylic acid) in chronic inflammatory bowel disease. In: Matern, S. (eds) Clinical Research in Gastroenterology 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-2488-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-2488-8_2

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-7622-7

  • Online ISBN: 978-94-009-2488-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation