Zileuton: clinical implications of 5-Lipoxygenase inhibition in severe airway disease.
The 5-Lipoxygenase pathway results in the formation of leukotrienes, including leukotriene B(4) (LTB(4)), 5-oxo-6E,8Z,11Z,14Z-eicosatetranoic acid and the cysteinyl leukotrienes (LTC(4), LTD(4) and LTE(4)) and activates all four leukotriene receptors, BLT1, BLT2, cysLT(1) and cysLT(2). Zileuton is the only commercially available inhibitor of the 5-Lipoxygenase pathway. In a number of clinical trials, zileuton has been shown to improve airway function and inflammation, asthma symptom control and quality of life in asthmatics. Given the important role that leukotrienes play in airway inflammation, zileuton provides an additional therapeutic option in the management of chronic, persistent asthma, particularly those asthmatics with more severe disease. In addition, zileuton has shown promise in a number of other conditions, including upper airway inflammatory conditions, dermatological disease and chronic obstructive pulmonary disease. The development of new formulations, including a controlled release tablet formulation for b.i.d. dosing and an intravenous preparation for acute asthma exacerbations may enhance clinical utility and expand therapeutic indications.
Berger
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Department of Pediatrics, Division of Allergy and Immunology, University of California, Irvine, Mission Viejo, CA, USA.
De Chandt
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Cairns
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000188:drug therapy; D004334:Drug Administration Schedule; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D016859:Lipoxygenase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D012220:Rhinitis / Q000188:drug therapy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016859:Lipoxygenase Inhibitors; C063449:zileuton; D006918:Hydroxyurea