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.