Although oral glucocorticoids are the treatment of choice for moderate to severe ulcerative pancolitis, their systemic side effects and adrenal suppression account for considerable morbidity. An oral glucocorticoid-conjugate (prodrug), budesonide-p-D-glucuronide, which is not absorbed in the small intestine but is hydrolysed by colonic bacterial and mucosal ,B-glucuronidase to release free budesonide into the colon was synthesised. The objective of this study was to compare treatment with budesonide-P-D-glucuronide with treatment with free budesonide by examining: (1) the healing of experimental colitis and (2) A new group of corticosteroids has recently been developed. In comparison with conventional corticosteroids, these drugs display a high degree of topical anti-inflammatory activity but do not show appreciable systemic activity. This unique activity ratio is achieved because a very high potency is coupled with rapid metabolism of the drug to products that have minimal or no biological activity. This rapid metabolism, also referred to as high first-pass liver metabolism, allows for a high therapeutic efficacy and high systemic tolerability.Budesonide is a member of this group of steroids which display high first-pass liver metabolism. Budesonide is a non-halogenated glucocorticoid structurally related to 16-alpha-hydroxyprednisolone.4 Administration of this drug via inhalation has proved effective in the treatment of asthma and rhinitis. It also presented a low adverse drug event profile.4Budesonide, given as an enema, has also proved superior to other glucocorticoids in the treatment of distal ulcerative colitis.5Budesonide has now been formulated into an enterocapsule preparation which allows the drug to bypass the upper gastrointestinal tract, thus facilitating delivery of the active compound to the terminal ileum.6 Unfortunately, it was found that less than 5%/o of the compound was available beyond the ileum and caecum.6 Therefore, while this compound would be useful for the treatment of small intestinal Crohn's disease,7 it is not likely to have an appreciable effect on colonic inflammatory bowel disease. In addition, a recent dose ranging study showed that effective doses of budesonide (9 mg/d) cause significant adrenal suppression.8Because of these problems, we designed and synthesised an orally administered, colonspecific budesonide prodrug (budesonide-,-D-glucuronide) with a delivery mechanism that would increase budesonide concentrations along the colon relative to systemic drug concentrations, thereby increasing colonic drug efficacy and decreasing systemic side effects.9 The advantage of colon-specific delivery has been already documented in the case of the non-steroidal anti-inflammatory agent 5-aminosalicylic acid. In that instance, the prodrugs sulphasalazine and olsalazine, from which the active drug is released in the colon by the action of microbial azoreductases, were used.10-'2