To review the pharmacology, pharmacokinetics, efficacy, and safety of oral budesonide (Entocort EC) in the treatment of mild to moderate Crohn's disease (CD).
Data Sources
The MEDLINE database (1966–December 2002) was searched using the key words budesonide and inflammatory bowel diseases and restricted to the English language. The references from relevant articles were also reviewed for additional citations.
Study Selection and Data Extraction
Articles and abstracts that evaluated oral budesonide for management of CD were considered, with emphasis on randomized, controlled clinical trials.
Data Synthesis
Budesonide's high potency at the glucocorticoid receptor and extensive first-pass hepatic metabolism result in a topical antiinflammatory effect on intestinal tissue, with minimal systemic glucocorticoid adverse effects. Clinical trials have demonstrated that budesonide is effective in the treatment of patients with mild to moderate CD of the ileum and ascending colon, with efficacy similar to prednisolone and superior to mesalamine. Long-term therapy with budesonide increased the duration of CD remission, but the effect was not sustained up to 1 year. Budesonide failed to prevent postsurgical relapse of CD. Adrenal suppression and glucocorticoid-related adverse effects have been reported at lower rates in patients treated with budesonide compared with prednisolone. Patients prescribed budesonide should be monitored for hepatic dysfunction and potential drug interactions.
Conclusions
Budesonide is an effective and relatively safe option for treatment of mild to moderate CD of the ileum and ascending colon.
SacharDBWalfishJInflammatory bowel diseases. In: BeersMHBerkowR, eds. The Merck manual. 17th ed. Whitehouse Station, NJ: Merck and Co., 1999:302–17.
2.
HanauerSBSandbornWPractice guidelines: management of Crohn's disease in adults. Am J Gastroenterol2001;96:635–43.
3.
SummersRWSwitzDMSessionsJTJrBecktelJMBestWRKernFJrNational Cooperative Crohn's Disease Study: results of drug treatment. Gastroenterology1979;77:847–69.
4.
SingletonJWLawDHKelleyMLJrMekhjianHSSturdevantRALNational Cooperative Crohn's Disease Study: adverse reactions to study drugs. Gastroenterology1979;77:870–82.
5.
BrogdenRNMcTavishDBudesonide: an updated review of its pharmacological properties, and therapeutic efficacy in asthma and rhinitis. Drugs1992;44:375–407.
6.
SpencerCMMcTavishDBudesonide: a review of its pharmacological properties and therapeutic efficacy in inflammatory bowel disease. Drugs1995;50:854–72.
7.
FriendDRReview article: issues in oral administration of locally acting glucocorticoids for treatment of inflammatory bowel disease. Aliment Pharmacol Ther1998;12:591–603.
8.
Bar-MeirSChowersYLavyAAbramovitchDSternbergALeichtmannGBudesonide versus prednisone in the treatment of active Crohn's disease. Gastroenterology1998;115:835–40.
9.
Package insert. Entocort EC (budesonide). Wilmington, DE: AstraZeneca, January 2002.
10.
DahlbergEThalénABrattsandRGustafssonJJohanssonURoempkeKCorrelation between chemical structure, receptor binding, and biological activity of some novel, highly active, 16α, 17α-acetal-substituted glucocorticoids. Mol Pharmacol1984;25:70–8.
11.
EdsbäckerSWollmerPNilssonANilssonMPharmacokinetics and gastrointestinal transit of budesonide controlled ileal release (CIR) capsules (abstract). Gastroenterology1993;104(4 suppl 1):A695.
12.
BrattsandROverview of newer glucocorticosteroid preparations for inflammatory bowel disease. Can J Gastroenterol1990;4:407–14.
13.
NaberAHJOlaisonGSmedhKJansenJBMJSjödahlRPharmacokinetics of budesonide controlled ileal release capsules in active Crohn's disease (abstract). Gastroenterology1996;110(4 suppl 1):A977.
14.
LundinPNaberTNilssonMEdsbäckerSEffect of food on the pharmacokinetics of budesonide controlled ileal release capsules in patients with active Crohn's disease. Aliment Pharmacol Ther2001;15:45–51.
15.
GreenbergGRFeaganBGMartinFSutherlandLRThomsonABRWilliamsCNOral budesonide for active Crohn's disease. N Engl J Med1994;331:836–41.
16.
TremaineWJHanauerSBKatzSWinstonBDLevineJGPerssonTBudesonide CIR capsules (once or twice daily divided-dose) in active Crohn's disease: a randomized placebo-controlled study in the United States. Am J Gastroenterol2002;97:1748–54.
17.
RutgeertsPLöfbergRMalchowHLamersCOlaisonGJewellDA comparison of budesonide with prednisolone for active Crohn's disease. N Engl J Med1994;331:842–5.
18.
CampieriMFergusonADoeWPerssonTNilssonLGOral budesonide is as effective as oral prednisolone in active Crohn's disease. Gut1997;41:209–14.
19.
ThomsenOOCortotAJewellDWrightJPWinterTVelosoFTA comparison of budesonide and mesalamine for active Crohn's disease. N Engl J Med1998;339:370–4.
20.
GreenbergGRFeaganBGMartinFSutherlandLRThomsonABRWilliamsCNOral budesonide as maintenance treatment for Crohn's disease: a placebo-controlled, dose-ranging study. Gastroenterology1996;110:45–51.
21.
LöfbergRRutgeertsPMalchowHLamersCDanielssonAOlaisonGBudesonide prolongs time to relapse in ileal and ileocaecal Crohn's disease. A placebo controlled one year study. Gut1996;39:82–6.
22.
FergusonACampieriMDoeWPerssonTNygardGOral budesonide as maintenance therapy in Crohn's disease - results of a 12 month study. Aliment Pharmacol Ther1998;12:175–83.
23.
FeaganBGreenbergGRLöfbergRFergusonAPerssonTBudesonide controlled ileal release prolongs remission in Crohn's disease (CD): a pooled analysis (abstract). Gastroenterology1997;112(4 suppl 1):A970.
24.
GreenJRBLoboAJGiafferMTravisSWatkinsHCMaintenance of Crohn's disease over 12 months: fixed versus flexible dosing regimen using budesonide controlled ileal release capsules. Aliment Pharmacol Ther2001;15:1331–41.
25.
CortotAColombelJFRutgeertsPLauritsenKMalchowHHämlingJSwitch from systemic steroids to budesonide in steroid dependent patients with inactive Crohn's disease. Gut2001;48:186–90.
26.
HellersGCortotAJewellDLeijonmarckCELöfbergRMalchowHOral budesonide for prevention of postsurgical recurrence in Crohn's disease. Gastroenterology1999;116:294–300.
27.
BestWRBecktelJMSingletonJWKernFJr.Development of a Crohn's Disease Activity Index. National Cooperative Crohn's Disease Study. Gastroenterology1976;70:439–44.
28.
Data on file. Wilmington, DE: AstraZeneca.
29.
D'HaensGVerstraeteACheynsKAerdenIBouillonRRutgeertsPBone turnover during short-term therapy with methylprednisolone or budesonide in Crohn's disease. Aliment Pharmacol Ther1998;12:419–24.
30.
CinoMGreenbergGRBone mineral density in Crohn's disease: a longitudinal study of budesonide, prednisone, and nonsteroid therapy. Am J Gastroenterol2002;97:915–21.
31.
SchoonEBollaniSMillsPIsraeliEFelsenbergDLjunghallSBudesonide versus prednisolone: effect on bone mineral density in patients with ileo-cecal Crohn's disease (abstract). Am J Gastroenterol2002;97(9 suppl 1):S272.
32.
HeeringaMZweersPAnaphylactic-like reaction associated with oral budesonide (letter). BMJ2000;321:927.
33.
SeidegardJReduction of the inhibitory effect of ketoconazole on budesonide pharmacokinetics by separation of their time of administration. Clin Pharmacol Ther2000;67:13–7.
34.
SeidegardJSimonssonMEdsbäckerSEffect of an oral contraceptive on the plasma levels of budesonide and prednisolone and the influence on plasma cortisol. Clin Pharmacol Ther2000;67:373–81.
35.
AhleGBBlumALMartinekJOnetaCMDortaGCushing's syndrome in an 81-year-old patient treated with budesonide and amiodarone. Eur J Gastroenterol Hepatol2000;12:1041–2.
36.
NilssonMEdsbäckerSLarssonPÖbergGBudesonide pharmacokinetics is not affected by omeprazole (abstract). Gut1995;37(suppl 2): A51.
37.
KundhalPZachosMHolmesJLGriffithsAMControlled ileal release budesonide in pediatric Crohn disease: efficacy and effect on growth. J Pediatr Gastroenterol Nutr2001;33:75–80.
38.
2002 Drug topics red book. Montvale, NJ: Medical Economics, 2002.
