Selective 5-lipoxygenase inhibition by zileuton in the treatment of relapsing ulcerative colitis

Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases

“…11-14 5-Aminosalicylates and glucocorticoids have been proven to have clinical value in treating IBD and to reduce LTB 4 levels in colonic mucosae and rectal dialysates of IBD patients. 15,16 Specific inhibitors of 5-LO similarly reduce LTB 4 in colonic mucosae, [17][18][19][20] and inhibitors of 5-LO and deletion of the 5-LO gene both markedly reduce colonic injury in rodent models. 21,22 However, in clinical trials of IBD patients, 5-LO inhibitors had mixed results.…”

Pharmacokinetic and pharmacodynamic analysis of a novel leukotriene biosynthesis inhibitor, MK‐0591, in healthy volunteers.

“…Therefore, leukotriene synthesis inhibitors are expected to be clinically efficacious in preventing or treating these diseases. In fact, A-64,077 a selective 5-lipoxygenase inhibitor, has been suggested to be effective in ulcerative colitis [17].…”

Evaluation of new therapies for inflammatory bowel disease

“…One way of attempting to obviate this difficulty is to assess the production of the target mediator very early (e.g. after a few hours) after administration of the test drug, before mucosal inflammation is likely to have been down-regulated by the agent by other mechanisms [48,49].…”

“…Cytokines and mediators released from the mucosa move across the dialysis membrane into the fluid in the bag; their concentration is measured after removal of the bag by analysis of its contents. This in vivo technique has been used to study the effects of drugs on release of eicosanoids [48,49,59], and to clarify drug pharmacokinetics by assay of their luminal concentrations [60]. Rectal dialysis is simple and safe.…”