Skip to main content
Log in

Budesonide

A Review of its Pharmacological Properties and Therapeutic Efficacy in Inflammatory Bowel Disease

  • Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Synopsis

Budesonide is a glucocorticoid with high topical activity, but low systemic bioavailability which results in reduced systemic effects in comparison with other glucocorticoids. To date, it has been evaluated for use in patients with inflammatory bowel disease when administered either orally as a controlled ileal release formulation or rectally as an enema.

In comparative trials, daily treatment with budesonide enema 2 mg/100ml for 4 weeks produced endoscopic remission or improvement in 46 to 84% of patients with active distal ulcerative colitis and/or proctitis and histological remission or improvement in 45 to 68%. In general, this regimen was a effective as regimens of hydrocortisone, methylprednisolone, prednisolone or mesalazine (5-aminosalicylic acid, mesalamine) enemas, but caused less suppression of plasma cortisol levels than the other glucocorticoids.

Oral treatment with controlled release budesonide 9 mg/day for 8 weeks produces clinical remission in 42 to 67% of patients with active Crohn’s disease of the ileum, ileocaecal region and/or ascending colon and significantly reduces Crohn’s disease activity index scores compared with baseline and placebo. Results of a quality-of-life questionnaire reflected these clinical improvements. Budesonide has similar efficacy to prednisolone. Response to budesonide is maintained after dosage tapering at 8 weeks. Compared with placebo, maintenance treatment with oral budesonide 3 or 6 mg/day increases the duration of remission in patients with Crohn’s disease, but does not appear to affect the 1-year relapse rate.

Thus, budesonide, administered rectally to patients with distal ulcerative colitis or proctitis or orally to patients with Crohn’s disease of the ileum, ileocaecal region and/or ascending colon, is a favourable option for the treatment of acute exacerbations of inflammatory bowel disease. Because of the low incidence of adverse glucocorticoid-related effects associated with oral budesonide, it may also be a useful agent for longer term maintenance therapy if further clinical trials confirm its efficacy in this indication.

Pharmacological Properties

Budesonide is a glucocorticoid used in the treatment of inflammatory bowel disease. It has greater topical anti-inflammatory activity than many other glucocorticoids, but does not reduce cortisol levels (a measure of systemic effect on adrenal function) to the same extent as methylprednisolone, prednisolone or hydrocortisone when administered orally or rectally. In fact, administration of budesonide 2 mg/100ml enema has no significant effect on basal plasma cortisol levels in patients with ulcerative colitis. Response to corticotrophin (adrenocorticotrophic hormone; ACTH) is also impaired to a lesser extent by rectal treatment with budesonide than with prednisolone. Similarly, oral budesonide 9 mg/day is associated with less impairment of adrenal function than oral prednisolone 40 mg/day (after 2 weeks tapered to 5 mg/day over 7 weeks), but does cause some adrenal suppression compared with placebo. A 1-year placebo-controlled study showed that decreases in ACTH-stimulated plasma cortisol levels induced by oral budesonide did not result in clinically important glucocorticoid-associated adverse effects in 105 patients with Crohn’s disease.

In general, treatment with oral budesonide 9 mg/day reduced mean erythrocyte sedimentation rate in patients with active Crohn’s disease, but did not significantly alter mean serum orosomucoid, C-reactive protein or albumin levels or plasma haptoglobin level. However, in 1 trial, budesonide therapy resulted in a 20% decrease in serum C-reactive protein level. Although both budesonide and prednisolone enema therapy induce small decreases in serum osteocalcin level from baseline, changes are greater in prednisolone recipients. Compared with oral prednisolone 40 mg/day (after 2 weeks tapered to 5 mg/day over 7 weeks), oral budesonide 9 mg/day (after 8 weeks tapered to 6 mg/day) produces smaller decreases in natural killer cell activity (by 22 to 30% vs 25 to 54%) after 2 and 4 weeks in patients with active Crohn’s disease.

Budesonide enema achieves adequate maximum retrograde colonic spread within 15 minutes in patients with distal ulcerative colitis. The drug has a systemic bioavailability of 9.3 to 15% and a mean absorption time of about 6 and 1.4 hours, respectively, when administered orally or rectally to healthy volunteers. In healthy volunteers and patients with ulcerative colitis, maximum plasma concentrations of 2.1 to 3 nmol/L are achieved 1.2 to 1.5 hours after rectal administration of budesonide 2 mg/100ml. Area under the plasma concentration-time curve increased after 28 days’ therapy, but other assessments showed that the drug did not accumulate with repeated administration. The controlled ileal release formulation of oral budesonide is predominantly absorbed in the ileum and ascending colon. Budesonide undergoes extensive first-pass metabolism via oxidative and reductive pathways in the liver to 2 major metabolites 6β-hydroxy-budesonide and 16α-hydroxy-prednisolone, which have considerably less glucocorticoid activity than the parent drug.

Therapeutic Efficacy

Budesonide has been incorporated into formulations for oral (controlled release) or rectal (enema) treatment of patients with inflammatory bowel disease, most commonly Crohn’s disease (affecting the ileum, ileocaecal region and/or ascending colon) or ulcerative colitis, respectively. Budesonide enema 2 mg/100ml generally has similar efficacy to hydrocortisone, methylprednisolone, prednisolone or mesalazine enemas and greater efficacy than placebo after 4 weeks of treatment. General well-being is also improved after 2 weeks’ treatment with budesonide enema in comparison with placebo. Budesonide enema produced endoscopic improvement faster than prednisolone enema in one of the larger studies, but not in another. Endoscopic remission or improvement occurred in 46 to 84% of patients treated with budesonide enema, while histological remission or improvement was achieved by 45 to 68% of patients enrolled in comparative trials.

Clinical remission is achieved by 42 to 67% of patients with active Crohn’s disease of the ileum, ileocaecal region and/or ascending colon following treatment with oral controlled ileal release budesonide 9 mg/day for 8 weeks. This drug regimen also significantly reduces Crohn’s disease activity index scores compared with baseline and placebo. Results of a quality-of-life questionnaire reflected these clinical improvements. Oral budesonide has a rapid effect in comparison with placebo, but results of comparisons with prednisolone were equivocal. However, oral budesonide generally has efficacy similar to that of prednisolone. Prior treatment with steroidal agents does not have a detrimental effect on response to oral budesonide. Budesonide dosages were generally tapered after 8 weeks of oral therapy and responses were maintained after dosage reductions. Maintenance treatment with budesonide 3 to 6 mg/day increases the duration of remission in patients with Crohn’s disease, but does not appear to significantly reduce the proportion of patients experiencing relapse after 1 year of treatment.

Tolerability

Budesonide enema is generally well tolerated: the most frequently experienced events (reported in ≤5% of patients) are gastrointestinal and include increased bowel frequency and colorectal bleeding. Haematuria, thromboembolism, acne and villous adenoma have been reported in 1 patient each. Laboratory abnormalities do not usually develop and no signs of significant adrenal suppression have been detected during treatment with budesonide enema.

In a large trial (n = 258) comparing oral controlled ileal release budesonide 3, 9 or 15 mg/day and placebo, similar proportion of patients in the active treatment and placebo groups experienced an adverse event or discontinued treatment because of these events. 41% of adverse events were gastrointestinal in nature, with dyspepsia and nausea being most commonly reported. Glucocorticoid-associated effects developed in a similar proportion of patients in each group (15 to 38%), but cushingoid facial features were more common with budesonide (7%) than with placebo (2%). Glucocorticoid-associated adverse effects, particularly cushingoid facial features, appear to occur more commonly during prednisolone therapy than during treatment with oral budesonide. Oral budesonide therapy does not appear to affect liver function tests, or to produce haematological and biochemical abnormalities when compared with placebo. In general, 6 to 12 months’ maintenance therapy with oral budesonide was not associated with significant adverse events. However, longer term trials are necessary to fully define the tolerability profile of budesonide.

Dosage and Administration

Budesonide enema 2 mg/100ml should be inserted rectally once daily at bedtime for the treatment of acute distal ulcerative colitis or proctitis. In most studies treatment was continued for 4 weeks. Clinical studies indicate that oral budesonide should be administered at a daily dose of 9mg for about 8 weeks for the treatment of active Crohn’s disease of the ileum, ileocaecal region and/or ascending colon.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Brogden RN, McTavish D. Budesonide: an updated review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis? Drugs 1992; 44 (3): 375–407.

    Article  PubMed  CAS  Google Scholar 

  2. van Rees EP, Soesatyo M, Palmen MJH, et al. Effect of local budesonide treatment in experimental inflammatory bowel disease [abstract]. Neth J Med 1993 Aug; 43: A24.

    Google Scholar 

  3. Boyd AJ, Sherman IA, Saibil FG. Budesonide reduces inflammation in a hamster model of ileitis [abstract]. Gastroenterology 1994 Apr; 106 (4) Suppl.: 1019

    Google Scholar 

  4. Clissold SP, Heel RC. Budesonide: a preliminary review of its pharmacodynamic properties and therapeutic efficacy in asthma and rhinitis. Drugs 1984; 28: 485–518.

    Article  PubMed  CAS  Google Scholar 

  5. Johansson S-Å, Andersson K-E, Brattsand R, et al. Topical and systemic glucocorticosteroid potencies of budesonide, beclomethasone dipropionate and prednisolone in man. Eur J Resp Dis 1982; 63 Suppl. 122: 74–82.

    Google Scholar 

  6. Bianchi Porro G, Prantera C, Campieri M, et al. Comparative trial of methylprednisolone and budesonide enemas in active distal ulcerative colitis. Eur J Gastroenterol Hepatol 1994; 6: 125–30.

    Article  Google Scholar 

  7. Danielsson 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  PubMed  CAS  Google Scholar 

  8. Danielsson Å, Löfberg R, Persson T, et al. A steroid enema, budesonide, lacking systemic effects for the treatment of distal ulcerative colitis or proctitis. Scand J Gastroenterol 1992; 27: 9–12.

    Article  PubMed  CAS  Google Scholar 

  9. Danielsson Å, Hellers G, Lyrenäs E, et al. A controlled randomized trial of budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Scand J Gastroenterol 1987 Oct; 22: 987–92.

    Google Scholar 

  10. Löfberg R, Østergaard Thomsen O, Langholz E, et al. Budesonide versus prednisolone retention enemas in active distal ulcerative colitis. Aliment Pharmacol Ther 1994 Dec; 8: 623–9.

    Google Scholar 

  11. Tarpila S, Turunen U, Seppälä K, et al. Budesonide enema in active haemorrhagic proctitis — a controlled trial against hydrocortisone foam enema. Aliment Pharmacol Ther 1994; 8: 591–5.

    Article  PubMed  CAS  Google Scholar 

  12. Campieri M, Ferguson A, Doe W, et al. Oral budesonide competes favourably with prednisolone in active Crohn’s disease [abstract]. Gastroenterology 1995; 108 (4) Suppl.: A790.

    Google Scholar 

  13. Greenberg GR, Feagan BG, Martin F. Oral budesonide for active Crohn’s disease. N Engl J Med 1994 Sep 29; 331: 836–41.

    Article  PubMed  CAS  Google Scholar 

  14. Löfberg R, Danielsson Å, Saide L. Oral budesonide in active Crohn’s disease. Aliment Pharmacol Ther 1993 Dec; 7: 611–6.

    Google Scholar 

  15. Rutgeerts P, Löfberg R, Malchow H, et al. A comparison of budesonide with prednisolone for active Crohn’s disease. N Engl J Med 1994 Sep 29; 331: 842–5.

    Article  PubMed  CAS  Google Scholar 

  16. Edsbäcker S, Larsson P, Nilsson M, et al. Budesonide controlled ileal release (CIR) capsules affect plasma cortisol less than prednisolone [abstract]. Gastroenterology 1995; 108 (4) Suppl.: A814.

    Article  Google Scholar 

  17. Thomsen Ø, Andersen T, Langholz E, et al. Lack of adrenal gland suppression with budesonide enema in active distal ulcerative colitis: a prednisolone-controlled 8-week study. Eur J Gastroenterol Hepatol 1994 Jun; 6: 507–11.

    Google Scholar 

  18. Hanauer S, Robinson M, for the US Budesonide Enema Study Group. Dose ranging study of budesonide enema in active distal ulcerative colitis [abstract]. Gastroenterology 1995; 108 (4) Suppl: A832.

    Article  Google Scholar 

  19. Roth M, Gross V, Scholmerich J, et al. Treatment of active Crohn’s disease with an oral slow-release budesonide formulation [letter]. Am J Gastroenterol 1993 Jun; 88: 968–9.

    Google Scholar 

  20. Greenberg GR, Feagan BG, Martin F, et al. Oral budesonide as maintenance treatment for Crohn’s disease: a placebo-controlled, dose-ranging study. Gastroenterology. In press

  21. van Ierssel AJHM, van der Sluys Veer A, Verspaget HW, et al. Budesonide and prednisolone suppress peripheral blood natural killer cells in Crohn’s disese. Aliment Pharmacol Ther 1995; 9: 173–8.

    Article  PubMed  Google Scholar 

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

    Google Scholar 

  23. Edsbäcker S, Johansson S-Å. Correlation between kinetic properties and clinical safety of budesonide enema [abstract no. PD 561]. World Congress of Gastroenterology. Sydney, Australia 1990.

  24. Dahlström K, Edsbäcker S, Conradson T-B. Rectal and oral bioavaliability of budesonide in man [abstract no. 297]. Hell J Gastroenterol 1992; 5 Suppl.

  25. Nilsson M, Edsbäcker S, Larsson P, et al. Dose-proportional kinetics of budesonide controlled ileal release (CIR) capsules. Lund, Sweden: Astra Draco AB, 1995. (Data on file).

    Google Scholar 

  26. Nilsson M, Edsbäcker S, Larsson P, et al. Dose-proportional kinetics of budesonide controlled ileal release capsules [abstract]. Gastroenterology 1995; 108 (4) Suppl: A885.

    Article  Google Scholar 

  27. Sjödahl R, Jansen J, Nilsson M, et al. Pharmacokinetics of budesonide CIR capsules in patients after single dose and after repeated administration of 4.5 mg twice daily. Lund, Sweden: Astra Draco AB, 1995. Report No.: 08-CR-3016. (Data on file).

    Google Scholar 

  28. Ryrfeldt Å, Andersson P, Edsbäcker S, et al. Pharmaeokinetics and metabolism of budesonide, a selective grucocorticoid. Eur J Resp Dis 1982; 63 Suppl. 122: 86–95.

    Google Scholar 

  29. Cvetkovic S, Edsbäcker S, Wollmer P, et al. Food does not alter site of absorption of budesonide from controlled ileal release capsules [abstract no. 524]. Gut 1995; 37 Suppl. 2 (2): A51.

    Google Scholar 

  30. Edsbäcker S, Andersson P, Lindberg C, et al. Liver metabolism of budesonide in rat, mouse, and man. Comparative aspects. Drug Metab Dispos 1987; 15: 403–11.

    PubMed  Google Scholar 

  31. Edsbäcker S, Jönsson S, Lindberg C, et al. Metabolic pathways of the topical glucocorticoid budesonide in man? Drug Metab Dispos 1983; 11 (6): 590–6.

    PubMed  Google Scholar 

  32. Andersson P, Ryrfeldt Å. Biotransformation of the topical glucocorticoids budesonide and beclomethasone 17α,21-dipropionate in human liver and lung homogenate. J Pharm Pharmacol 1984; 36: 763–5.

    Article  PubMed  CAS  Google Scholar 

  33. Danish Budesonide Study Group. Budesonide enema in distal ulcerative colitis. A randomized dose-response trial with prednisolone enema as positive control. Scand J Gastroenterol 1991; 26: 1225–30.

    Article  Google Scholar 

  34. Löfberg R. Budesonide enema in therapy-resistant distal UC and colonic CD [abstract]. New aspects of the treatment of inflammatory bowel disease. Chester: Adis International, 1991: 14.

    Google Scholar 

  35. Saide LG, Conradson TB. Compassionate use of budesonide enema in inflammatory bowel disease. A retrospective study in 110 patients. AB Astra Draco, 1995. (Data on file).

  36. Lamers C, Meijer J, Engels L, et al. Comparative study of the topically acting glucocorticosteroid budesonide and 5-aminosalicylic acid enema therapy of proctitis and proctosigmoiditis [abstract]. Gastroenterology 1991; 100 (5): A223.

    Google Scholar 

  37. Lemann M, Rutgeerts P, van Heuvertzwijn R, et al. Comparison of budesonide enema and 5-ASA enema in the treatment of active distal ulcerative colitis [abstract]. 1st United European Gastroenterology Week, Athens, Sep 25–27, 1991.

  38. Bayless T, Sninsky C, for the US Budesonide Enema Study Group. Budesonide enema is an alternative to hydrocortisone enema in active distal ulcerative colitis [abstract]. Gastroenterology 1995; 108 (4) Suppl.: A778.

    Article  Google Scholar 

  39. Caesar I, Gross V, Roth M, et al. Treatment of active Crohn’s ileocolitis with oral pH-modified budesonide. Z Gastroenterol 1995; 33: 247–50.

    PubMed  CAS  Google Scholar 

  40. Gross V, Andus T, Caesar I, et al. Oral pH-modified release budesonide vs 6-methylprednisolone in active Crohn’s Disease [abstract]. Gastroenterology 1995; 108 (4) Suppl: A828.

    Google Scholar 

  41. Katz J. The course of inflammatory bowel disease? Med Clin North Am 1994; 78 (6): 1275–80.

    PubMed  CAS  Google Scholar 

  42. Wolman SL, Greenberg GR. Oral budesonide in active Crohn’s disease: an initial experience [abstract]. Gastroenterology 1991 May; 100 Suppl.: 263

    Google Scholar 

  43. Löfberg R, Danielsson Å, Nilsson Å, et al. Oral budesonide is comparable to prednisolone in active ulcerative colitis but causes no suppression of plasma cortisol [abstract 178P]. 10th Congress of Gastroenterology October 207, 1994.

  44. Löfberg R, Rutgeerts P, Malchow H. Budesonide CIR for maintenance of remission in ileocecal Crohn’s disease. A European multicenter placebo controlled trial for 12 months [abstract no. 90]. 10th World Congresses of Gastroenterology 1994: 13.

  45. Novacek G, Kleinberger M, Vogelsang H, et al. Budesonide in glucocorticoid dependent chronic active Crohn’s disease; a pilot study. Z Gastroenterol 1995; 33: 251–4.

    PubMed  CAS  Google Scholar 

  46. Gross V, Andus T, Ecker KW, et al. Oral pH-modified release budesonide for maintenance of steroid induced remission in Crohn’s Disease — an anterim analysis [abstract]. Gastroenterology 1995; 108 (4) Suppl: A828.

    Google Scholar 

  47. Gibson PR. Inflammatory bowel disease? Current concepts in pathogenesis and therapy. Clin Immunother 1994; 2 (2): 134–60.

    Google Scholar 

  48. Binder y. The current understanding of inflammatory bowel disease? Res Clin Forum 1993; 15 (5): 11–6.

    Google Scholar 

  49. Ekbom A, Helmick C, Zack M, et al. The epidemiology of inflammatory bowel disease: a large, population-based study in Sweden. Gastroenterology 1991; 100: 350–8.

    PubMed  CAS  Google Scholar 

  50. Langholz E, Munkholm P, Nielsen OH, et al. Incidence and prevalence of ulcerative colitis in Copenhagen county from 1962 to 1987. Scand J Gastroenterol 1991; 26: 1247–56.

    Article  PubMed  CAS  Google Scholar 

  51. Jewell DP. The new steroids: clinical experience in ulcerative colitis. Mt Sinai J Med 1990 Oct; 57: 293–6.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Various sections of the manuscript reviewed by: S. Bank, Division of Gastroenterology, Long Island Jewish Medical Center, New Hyde Park, New York, USA; G. Bianchi Porro, Gastrointestinal Unit, Ospedale ‘L. Sacco’, Milan, Italy; V. Binder, Department of Medical Gastroenterology, Herlev Hospital/University of Copenhagen, Herlev, Denmark; M. Campteri, Istituto di Clinica Medica e Gastroenterologia, Clinica Medica Generale e Terapia Medica, Policlinico S. Orsola, Bologna, Italy; Å Danielsson, Section for Gastroenterology & Hepatology, Department of Medicine, Umeå University, Umeå, Sweden; G.R. Greenberg, Division of Gastroenterology, Mount Sinai Hospital, Toronto, Ontario, Canada; D.P. Jewell, Gastroenterology Unit, Radcliffe Infirmary, Oxford, England; J.E. Kellow, University of Sydney Department of Medicine, Royal North Shore Hospital, St Leonards, New South Wales, Australia; V. Mani, Department of Gastroenterology, Leigh Infirmary, Leigh, England; T. Miwa, School of Medicine, Tokai University, Boseidai, Isehara, Kanagawa, Japan; J.M. Rhodes, University Department of Medicine, Liverpool University, Liverpool, England; P. Rutgeerts, Department of Gastroenterology, Leuven University Hospital, Leuven, Belgium; W. Selby, Royal Prince Alfred Hospital Medical Centre, Newton, New South Wales, Australia; S. Tarpila, The Deaconess Hospital, The Deaconess Institute in Helsinki, Helsinki, Finland.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spencer, C.M., McTavish, D. Budesonide. Drugs 50, 854–872 (1995). https://doi.org/10.2165/00003495-199550050-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-199550050-00006

Keywords

Navigation