Skip to main content
SpringerLink
Log in

Pharmakokinetische Daten für verschiedene 5-Aminosalicylsäure- und Budesonidpräparate

Pharmacokinetic properties of various preparations of 5-Aminosalicylic acid (5-ASA) and budesonide

  • Published:
Medizinische Klinik Aims and scope Submit manuscript

Zusammenfassung

□ Verschiedene oral und rektal zu verabreichende 5-Aminosalicylsäure- (5-ASA-) und Budesonidpräparate wurden entwickelt, um damit am Ort der Entzündung (Dünn- und/oder Dickdarm) möglichst hohe Wirkstoffkonzentrationen zu erzielen, die idealerweise nur eine topische Wirkung zur Folge haben. Dieses „Drug-targeting“-Konzept konnte einerseits durch galenische Hilfsmittel, andererseits durch die pharmakokinetischen Eigenschaften beider Wirkstoffe, insbesondere aufgrund der hohen intestinalen und hepatischen präsystemischen Elimination, erfolgreich bei der Therapie von Morbus Crohn und Colitis ulcerosa umgesetzt werden.

□ Diese Übersicht beschreibt die verschiedenen pharmakokinetischen Faktoren und (patho-)physiologischen Störgrößen, welche einen Einfluß auf die Bereitstellung und biologische Verfügbarkeit der verschiedenen 5-ASA- bzw. Budesonidpräparate haben.

Abstract

□ Different orally and rectally applicable forms of 5-ASA and budesonide have been developed to achieve sufficient high concentrations of the active moieties at the site of inflammation (small and/or large bowel) and to limit the systemic action of the drugs. This concept of drug targeting could be accomplished by both special galenic formulations and by utilizing the pharmacokinetic properties of the agents especially their high intestinal and hepatic presystemic elimination. Thus, 5-ASA and budesonide represent drugs of first choice in the treatment of Crohn’s disease and ulcerative colitis.

□ This review describes the various pharmacokinetic and (patho)physiologic factors and their impact on drug delivery and biological availability of the different 5-ASA and budesonide preparations.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Allgayer H, Niels O, Ahnfelt NO, et al. Colonic N-acetylation of 5-aminosalicylic acid in inflammatory bowel disease. Gastroenterology 1989;97:38–41.

    PubMed  CAS  Google Scholar 

  2. Almer S, Norlander B, Ström M, et al. Steady-state pharmacokinetics of a new 4-gram 5-aminosalicylic acid retention enema in patients with ulcerative colitis in remission. Scand J Gastroenterol 1991;26:327–35.

    Article  PubMed  CAS  Google Scholar 

  3. Batham AK. A pharmacokinetic and radiographic study of 5-aminosalicylic acid position-release tablets. Curr Ther Res 1991;50:101–10.

    CAS  Google Scholar 

  4. Bodegraven AA van, Boer RO, Lourens J, et al. Distribution of mesalazine enemas in active and quiescent ulcerative colitis. Aliment Pharmacol Ther 1996;10:327–32.

    Article  PubMed  Google Scholar 

  5. Bondesen S, Hegnhøj J, Larsen F, et al. Pharmacokinetics of 5-aminosalicylic acid in man following administration of intravenous bolus and per os slow-release formulation. Dig Dis Sci 1991;36:1735–40.

    Article  PubMed  CAS  Google Scholar 

  6. Brogden RN, Sorkin EM. Mesalazine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in chronic inflammatory bowel disease. Drugs 1989;38:500–23.

    Article  PubMed  CAS  Google Scholar 

  7. Campieri M, Corbelli, C, Gionchetti P, et al. Spread and distribution of 5-ASA colonic foam and 5-ASA enema in patients with ulcerative colitis. Dig Dis Sci 1992;37: 1890–7.

    Article  PubMed  CAS  Google Scholar 

  8. Christensen LA, Fallingborg J, Jacobsen BA, et al. Pharmakokinetik der oral verabreichten 5-Aminosalicylsäure (Mesalazin)-Präparate: Unterschiede und mögliche klinische Auswirkungen. Chirurg Gastroenterol 1993;9:Suppl 1:38–43.

    Article  Google Scholar 

  9. Christensen LA, Fallingborg J, Abildgaard K, et al. Topical and systemic availability of 5-aminosalicylate: comparisons of three controlled release preparations in man. Aliment Pharmacol Ther 1990;4:523–33.

    PubMed  CAS  Google Scholar 

  10. Dale K, Elvin AT, Morill B, et al. Effect of food coadministration on 5-aminosalicylic acid oral suspension bioavailability. Clin Pharmacol Ther 1990;48:26–33.

    Google Scholar 

  11. Danielson Å, Edsbäcker S, Löfberg R, et al. Pharmacokinetics of budesonide enema in patients with distal ulcerative colitis or proctitis. Aliment Pharmacol Ther 1993;7:401–7.

    Article  Google Scholar 

  12. Edsbäcker S, Wollmer P, Nilsson M. Pharmacokinetics and gastrointestinal transit of budesonide controlled ileal release (CIR) capsules. Gastroenterology 1993; 104, No. 4, Suppl., A 695.

  13. Fischer C, Maier K, Stumpf E, et al. Disposition of 5-aminosalicylic acid, the active metabolite of sulphasalazine, in man. Eur J Clin Pharmacol 1983;25:511–5.

    Article  PubMed  CAS  Google Scholar 

  14. Gionchetti P, Campieri M, Belluzzi A, et al. Bioavailability of single and multiple doses of a new oral formulation of 5-ASA in patients with inflammatory bowel disease and healthy volunteers. Aliment Pharmacol Ther 1994; 8:535–40.

    Article  PubMed  CAS  Google Scholar 

  15. Goebell H, Klotz U, Nehlsen B, et al. Oro-ileal transit of slow release 5-aminosalicylic acid. Gut 1993;34:669–75.

    Article  PubMed  CAS  Google Scholar 

  16. Hanauer SB. Inflammatory bowel disease. N Engl J Med 1996;334:841–8.

    Article  PubMed  CAS  Google Scholar 

  17. Hardy JC, Healey JNC, Reynolds JR. Evaluation of an enteric-coated delayed-release 5-aminosalicylic acid tablet in patients with inflammatory bowel disease. Aliment Pharmacol Ther 1987;1:273–80.

    PubMed  Google Scholar 

  18. Hardy JC, Healey JNC, Lee SW, et al. Gastrointestinal transit of an enteric-coated delayed-release 5-aminosalicylic acid tablet. Aliment Pharmacol Ther 1987;1:209–16.

    PubMed  CAS  Google Scholar 

  19. Hardy JC, Harvey WJ, Sparrow RA, et al. Localization of drug release sites from an oral sustained-release formulation of 5-ASA (Pentasa®) in the gastrointestinal tract using gamma scintigraphy. J Clin Pharmacol 1993; 33:712–8.

    PubMed  CAS  Google Scholar 

  20. Ireland A, Priddle JD, Jewell DP, Comparison of 5-aminosalicylic acid and N-acetylaminosalicylic acid uptake by the isolated human colonic epithelial cell. Gut 1992; 33:1343–7.

    Article  PubMed  CAS  Google Scholar 

  21. Jacobsen BA, Abildgaard K, Rasmussen HH, et al. Availability of mesalazine (5-aminosalicylic acid) from enemas and suppositories during steady-state conditions. Scand J Gastroenterol 1991;26:374–8.

    Article  PubMed  CAS  Google Scholar 

  22. Järnerot G. Newer 5-aminosalicylic acid based drugs in chronic inflammatory bowel disease. Drugs 1989;37:73–86.

    Article  PubMed  Google Scholar 

  23. Jönsson G, Åström A, Andersson P. Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver. Drug Metab Disp 1995;23:137–42.

    Google Scholar 

  24. Klotz U. Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet 1985;10:285–302.

    Article  PubMed  CAS  Google Scholar 

  25. Klotz U. Pharmacokinetic properties of 5-aminosalicylic acid (mesalazine). In: Goebell H, Peskar BM, Malchow H, eds. Inflammatory bowel diseases — basic research and clinical implications. Lancaster-Boston-The Hague-Dordrecht: MTS Press, 1988:339–47.

    Google Scholar 

  26. Klotz U. Drug metabolism in the intestinal wall. In: Blum HE, Bode C, Bode JC, et al. eds. Gut and the liver. Dordecht-Boston-London: Kluwer, 1998:163–76.

    Google Scholar 

  27. Klotz U, Maier KE. Pharmacology and pharmacokinetics of 5-aminosalicylic acid. Dig Dis Sci 1987;32:46S-50S.

    Article  PubMed  CAS  Google Scholar 

  28. Laursen LS, Stokholm M, Bukhave J, et al. Disposition of 5-aminosalicylic acid by olsalazine und three mesalazine preparations in patients with ulcerative colitis: Comparison of intraluminal colonic concentrations, serum values, and urinary excretion. Gut 1990;31:1271–6.

    Article  Google Scholar 

  29. Layer PH, Goebell H, Keller J, et al. Delivery and fate of oral mesalamine microgranules within the human small intestine. Gastroenterology 1995;108:1427–33.

    Article  PubMed  CAS  Google Scholar 

  30. Löfberg R. Oral formulation of budesonide for IBD. Res Clin Forums 1993;15:91–6.

    Google Scholar 

  31. de Mey C, Meineke I. Prandial and diurnal effects on the absorption of orally administered enteric coated 5-aminosalicylic acid (5-ASA). Br J Clin Pharmacol 1992;33:179–82.

    PubMed  Google Scholar 

  32. Möllmann HW. Pharmacological basis for the use of non-systemic oral and rectal steroids in inflammatory bowel disease. In: Tytgat GNJ, Bartelsman FWM, Deventer SHJ van, eds. Inflammatory bowel diseases. Dordrecht-Boston-London: Kluwer, 1995:633–46.

    Google Scholar 

  33. Möllmann HW, Hochhaus G, Tromm A, et al. Pharmacokinetics and pharmacodynamics of budesonide-pH-modified release capsules. In: Möllmann HW, May B, eds. Glucocorticoid therapy in chronic inflammatory bowel disease-from basic principles to rational therapy. Dordrecht-Boston-London: Kluwer, 1996: 107–20.

    Google Scholar 

  34. Myers B, Evans DNW, Rhodes J, et al. 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 1987;28:196–200.

    Article  PubMed  CAS  Google Scholar 

  35. Nilsson M, Edsbäcker S, Larsson P, et al. Dose-proportional kinetics of budesonide controlled ileal release capsules. Gastroenterology 1995;108:A885.

    Google Scholar 

  36. Nolen H III, Fedorak RN, Friend DR. Budesonide-β-D-glucuronide: a potential prodrug for treatment of ulcerative colitis. J Pharm Sci 1995;84:677–81

    Article  PubMed  CAS  Google Scholar 

  37. Norlander B, Gotthard R, Ström M. Pharmacokinetics of a 5-aminosalicylic acid enteric-coated tablet and suppository dosage form. Aliment Pharmacol Ther 1989;3:333–42.

    Article  PubMed  CAS  Google Scholar 

  38. Norlander B, Gotthard R, Ström M. Steady-state pharmacokinetics of enteric coated 5-armino-salicylic acid tablets in healthy volunteers and in patients with Crohn’s disease or ulcerative colitis. Aliment Pharmacol Ther 1991;5:291–300.

    Article  PubMed  CAS  Google Scholar 

  39. Nyman-Pantelidis M, Nilsson A, Wagner ZG, et al. Pharmacokinetics and retrograde colonic spread of budesonide enemas in patients with distal ulcerative colitis. Aliment Pharmacol Ther 1994;8:617–22.

    Article  PubMed  CAS  Google Scholar 

  40. Rhodes J, Thomas G, Evans BK. Inflammatory bowel disease management. Some thoughts on future drug developments. Drugs 1997;53:189–94.

    Article  PubMed  CAS  Google Scholar 

  41. Rijk MCM, van Schaik A, van Tongeren JHM. Disposition of mesalazine from mesalazine-delivering drugs in patients with inflammatory bowel disease, with and without diarrhoea. Scand J Gastroenterol 1992;27:863–8.

    Article  PubMed  CAS  Google Scholar 

  42. Rijk MCM, van Hogezard RA, van Schaik A, et al. Disposition of 5-aminosalicylic acid from 5-arminosalicylicdelivering drugs during accelerated intestinal transit in healthy volunteers. Scand J Gastroenterol 1989;24:1179–85.

    Article  PubMed  CAS  Google Scholar 

  43. Riley SA, Tavares IA, Bishai PM, et al. Mesalazine release from coated tablets: effect of dietary fibre. Br J Clin Pharmacol 1991;32:248–50.

    PubMed  CAS  Google Scholar 

  44. Ryrfeldt Å, Edsbäcker S, Pauwels R. Kinetics of the epimeric glucocorticoid budesonide. Clin Pharmacol Ther 1984;35:525–30.

    PubMed  CAS  Google Scholar 

  45. Schoonjans R, de Vos M, Schelfhout A-M, et al. Distribution and concentrations of 5-aminosalicylic acid in rectosigmoid biopsy specimens after rectal administration. Dis Colon Rectum 1996;39:788–93.

    Article  PubMed  CAS  Google Scholar 

  46. Spencer CM, McTavish D. Budesonide. A review of its pharmacological properties and therapeutic efficacy in inflammatory bowel disease. Drugs 1995;50:854–72.

    Article  PubMed  CAS  Google Scholar 

  47. Thiessen A, Thomson ABR. Review article: older systemic and newer topical glucocorticosteroids and the gastrointestinal tract. Aliment Pharmacol Ther 1996;10:487–96.

    Article  Google Scholar 

  48. Tiel-van Buul MMC, Mulder CJ, van Royen EA, et al. Retrograde spread of mesalazine (5-aminosalicylic acid)-containing enema in patients with ulcerative colitis. Clin Pharmacokinet 1991;20:247–51.

    Article  PubMed  CAS  Google Scholar 

  49. Vitti RA, Meyers F, Knight LC, et al. Quantitative distribution of radiolabeled 5-aminosalicylic acid enemas in patients with left-sided ulcerative colitis. Dig Dis Sci 1989;34:1792–7.

    Article  PubMed  CAS  Google Scholar 

  50. Vos M de, Verdievel H, Schoonjans R, et al. Concentrations of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations. Gut 1992;33:1338–42.

    Article  PubMed  Google Scholar 

  51. Whiting GW, Lau J, Kupelnick B, et al. Trends in inflammatory bowel disease therapy: a meta-analytic approach. Can J Gastroenterol 1995;9:405–11.

    Google Scholar 

  52. Williams CN, Haber G, Aquino JA, Double-blind, place-bo-controlled evaluation of 5-ASA suppositories in active distal proctitis and measurement of extent of spread using99mTc-labeled 5-ASA suppositories. Dig Dis Sci 1987;32:71S-5S.

    Article  PubMed  CAS  Google Scholar 

  53. Wiltink EHH, Mulder JJ, Stolk LML, et al. Absorption of oral mesalazine-containing preparations and the influence of famotidine on the absorption. Scand J Gastroenterol 1990;25:579–84.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

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

    Ulrich Klotz

Authors
  1. Ulrich Klotz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ulrich Klotz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klotz, U. Pharmakokinetische Daten für verschiedene 5-Aminosalicylsäure- und Budesonidpräparate. Med Klin 94 (Suppl 1), 16–22 (1999). https://doi.org/10.1007/BF03042028

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03042028

Schlüsselwörter

Key Words

Search

Navigation