Targeted delivery of
5-aminosalicylic acid to the small intestine and colon by controlled-release or azo-bonded compounds potentially offers treatment for ileal
Crohn's disease as well as
ulcerative colitis. The pharmacokinetics of
sulphasalazine and aminosalicylate derivatives have been discussed and potential modes of action reviewed. These include actions on epithelial cell-surface receptors, cellular events and barrier function. Evidence for an influence of
salicylates on circulating and tissue inflammatory cells is presented, as well as actions on adhesion molecules, chemotactic
peptides,
eicosanoids,
cytokines and reactive
oxygen metabolites. The precise mechanism remains unknown, but a pluripotential mode of action is an advantage when influencing the network of events that constitutes chronic
inflammation. Controlled clinical trials of
salicylates in
ulcerative colitis and
Crohn's disease have been reviewed. Their main role remains as maintenance
therapy for
ulcerative colitis, but relatively high doses of
controlled-release preparations benefit patients with ileal
Crohn's disease, following resection, or those who have recently relapsed. Finally, issues of clinical relevance have been addressed, including the choice of
salicylate and safety, indications for initiating
therapy, dose and
duration of treatment, role in managing refractory
colitis and future developments.