COX-LOX inhibition: current evidence for an emerging new therapy.
Safe and effective drug treatment is an important objective of all doctors. In the treatment of arthritis, non-steroidal anti-inflammatory drugs offer effective treatment but safety is significantly limited, largely due to gastrointestinal toxicity. Attention has recently focused on exploiting increased knowledge of metabolism of arachidonic acid to allow the development of safer anti-inflammatory drugs. Dual inhibitors of cyclo-oxygenase and lipoxygenase are planned. These drugs may inhibit formation of both prostaglandins and leukotrienes. This review outlines the salient features of cyclo-oxygenase and lipoxygenase metabolism of arachidonic acid. The role of the eicosanoids in mediating inflammation and gastrointestinal integrity is delineated. Evidence is presented regarding action of licofelone, one COX/LOX inhibitor that is currently in advanced stages of clinical trials. This review examines the hypothesis that licofelone is an effective anti-inflammatory agent that does not cause peptic damage.
Skelly
M M
MM
Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Hawkey
C J
CJ
D000085:Acetates / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism*; D001168:Arthritis / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004285:Dogs; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D015289:Leukotrienes / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D023421:Models, Animal; D010437:Peptic Ulcer / Q000139:chemically induced; D011453:Prostaglandins / Q000378:metabolism; D011758:Pyrroles / Q000627:therapeutic use; D051381:Rats; D012756:Sheep
D000085:Acetates; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D011453:Prostaglandins; D011758:Pyrroles; D016718:Arachidonic Acid; C088092:licofelone