Budesonide: Teaching an Old Dog New Tricks for Inflammatory Bowel Disease Treatment

Abstract

Crohn's disease and ulcerative colitis are chronic relapsing inflammatory bowel diseases with extremely great variability in presentation and clinical course. For many decades, corticosteroids and aminosalicylates have been the mainstay of the treatment for both Crohn's disease and ulcerative colitis, for the induction and maintenance of remission, respectively. The main limiting factors for the repeated use of corticosteroids or the use as a maintenance treatment are the very high prevalence of systemic side effects, together with the possibility of developing dependency on and/or resistance to the drug, which are reported in more than one third of patients with inflammatory bowel disease. In the last decade, a number of corticosteroids with enhanced topical activity and low systemic activity have been developed. Among them, budesonide and beclomethasone dipropionate are the most used for the treatment of the inflammatory bowel diseases. Indeed, budesonide is the drug of choice for the treatment of ileo(-cecal) active Crohn's disease with mild-to-moderate activity, due to controlled ileal release. Budesonide foam and/or enemas are also efficacious in the treatment of left-sided/distal ulcerative colitis. Gastro-resistant, extended release tablets characterized by a multimatrix structure (i.e. MMX-budesonide), have also been developed to allow uniform release along the length of the colon. This paper reviews the mechanism-of-action, safety and efficacy of budesonide in the treatment of inflammatory bowel disease.

The effect of orally administered Budesonide on the hypothalamic-pituitary-adrenal axis in dogs with inflammatory bowel disease

“…The above process produces two main metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, which are characterised by negligent glucocorticosteroid activity and are excreted by the kidneys in free or conjugated form. Non-metabolizable Budesonide is undetectable in urine (Angelucci et al 2008).…”

“…Budesonide is a synthetic, halogen-free glucocorticosteroid analogue which is metabolised to a form that shows an absence of or minimal steroid activity (Tumulty et al 2004;Angelucci et al 2008). After absorption, which can be complete, Budesonide undergoes first-pass metabolism in the liver (80-90%; Spencer and McTavish 1995;Miller-Larsson et al 2001), which is catalysed by the CYP3A4 isoenzyme of cytochrome p-450, secreted by hepatocytes and intestinal epithelial cells (Jonsson et al 1995;Thomsen et al 1998;Tumulty et al 2004;Angelucci et al 2008).…”

“…After absorption, which can be complete, Budesonide undergoes first-pass metabolism in the liver (80-90%; Spencer and McTavish 1995;Miller-Larsson et al 2001), which is catalysed by the CYP3A4 isoenzyme of cytochrome p-450, secreted by hepatocytes and intestinal epithelial cells (Jonsson et al 1995;Thomsen et al 1998;Tumulty et al 2004;Angelucci et al 2008). The above process produces two main metabolites, 6β-hydroxybudesonide and 16α-hydroxyprednisolone, which are characterised by negligent glucocorticosteroid activity and are excreted by the kidneys in free or conjugated form.…”

“…The mechanism of glucocorticosteroid activity in the treatment of IBD has not been fully elucidated. GCs probably exert anti-inflammatory effects by inhibiting the release of inflammatory mediators and suppressing reactions that involve cytokines (Angelucci et al 2008). Despite their therapeutic benefits, glucocorticosteroids exert serious side-effects after long-term administration, which include iatrogenic hyperadrenocorticism and lower activity Supported by the Ministry of Science and Higher Education, Poland (Grant No.…”

Clinical, endoscopic and histopathological evaluation of the efficacy of budesonide in the treatment of inflammatory bowel disease in dogs

“…The mechanism of glucocorticosteroid activity in the treatment of IBD has not been fully elucidated. Glucocorticosteroids probably exert anti-inflammatory effects by inhibiting the release of inflammatory mediators and suppressing reactions that lead to the production of cytokines (Angelucci et al 2008). Despite their therapeutic…”