LEUKOTRIENE-RECEPTOR ANTAGONISTS AND 5-LIPOXYGENASE INHIBITORS IN ASTHMA

OBJECTIVE: To familiarize readers with a potentially new class of comp ounds for treating asthma. Background information on leukotrienes is p rovided in addition to an indepth review of pertinent clinical trials. DATA SOURCES: Information was obtained from controlled clinical trial s, abstracts, and review articles identified through a MEDLINE search of English-language articles. STUDY SELECTION: Emphasis was placed on early clinical trials that showed some benefit with these compounds as well as more recent studies using newer agents that produced more pro mising results. DATA EXTRACTION: Information regarding leukotriene bio chemistry was extracted from basic science research and data from huma n studies were evaluated by the authors according to patient selection , study design, methodology, and therapeutic response. DATA SYNTHESIS: Leukotrienes have a pathophysiologic role in asthma. Two distinct but pharmacologically similar classes of leukotriene inhibitors are curre ntly being clinically evaluated. These are leukotriene receptor antago nists and 5-lipoxygenase inhibitors. Early clinical trials with these agents yielded unfavorable results primarily because of lack of drug p otency and selectivity, poor patient tolerance, and possibly the route of administration. Subsequent studies with more potent and selective agents have further implicated leukotrienes as biochemical mediators i n asthma and, consequently, have shown promising clinical outcomes wit h respect to pulmonary function testing and patient tolerance. CONCLUS IONS: Advancements in the pathogenesis of asthma are beginning to defi ne a role for the leukotrienes. Although more studies are needed to as sess the efficacy of leukotriene inhibitors, recent clinical trials us ing leukotriene-receptor antagonists and 5-lipoxygenase inhibitors ind icate a potential for the expansion of therapeutic regimens currently used in the treatment of asthma.