Disease relevance of montelukast

• CONCLUSIONS: As compared with placebo, once-daily treatment with montelukast provided significant protection against exercise-induced asthma over a 12-week period [1].
• Marked peripheral edema associated with montelukast and prednisone [2].
• RESULTS: Montelukast improved airway obstruction (forced expiratory volume in 1 second, morning and evening peak expiratory flow rate) and patient-reported end points (daytime asthma symptoms, "as-needed" beta-agonist use, nocturnal awakenings) (P<.001 compared with placebo) [3].
• RESULTS: More significant decreases occurred in urticaria activity scores with montelukast therapy compared with those with placebo therapy (P <.001) [4].
• Montelukast alone and loratadine alone caused modest improvements in rhinitis end points [5].

High impact information on montelukast

• RESULTS: At 12 weeks, montelukast therapy offered significantly greater protection against exercise-induced bronchoconstriction than placebo therapy (expressed as the percentage of inhibition of the end points), as evidenced by the improvement in the area under the FEV1 curve (degree of inhibition, 47.4 percent; P=0.002) [1].
• OBJECTIVE: To evaluate the effect of 8 weeks of therapy with salmeterol aerosol or montelukast on exercise-induced bronchoconstriction in adults with asthma [6].
• The synergistic effect of LTC(4) and IL-13 on eotaxin production was abolished by CysLT1R antagonists pranlukast and montelukast [7].
• However, the response was not affected by chelerytrine chloride (protein kinase C inhibitor) or montelukast (cysteinyl leukotriene receptor antagonist) [8].
• We describe here the use of an eosinophil stabilising agent Montelukast for the symptomatic relief of these patients [9].

Chemical compound and disease context of montelukast

• Thus, montelukast and budesonide attenuated allergen-induced asthmatic responses, airway hyperresponsiveness, and sputum eosinophilia, although combination treatment did not provide greater antiinflammatory effects than either drug alone [10].
• In OVA-treated mice, airway eosinophil infiltration and goblet cell metaplasia were reduced by either montelukast or dexamethasone alone [11].
• BACKGROUND: Some leukotriene receptor antagonists, such as zafirlukast and montelukast, have been associated with systemic eosinophilia, with interest focused on Churg-Strauss syndrome (CSS) [12].
• OBJECTIVES: We sought to determine whether treatment with montelukast would improve symptoms and decrease both peripheral blood and tissue eosinophilia (TE) in a patients with steroid-dependent EG for 20 years complicated by esophageal stricture [13].
• INTRODUCTION: The effect of montelukast therapy on bronchial hyperreactivity (BHR) as measured by the methacholine challenge test in preschool children has not yet been reported [14].

Biological context of montelukast

• RESULTS: Montelukast given concomitantly with loratadine caused significant improvement in percentage of change from baseline in forced expiratory volume in 1 second (FEV(1)) compared with montelukast alone (13.86% vs 9.72%; P =.001) [15].
• We studied the effects of telithromycin, montelukast, and the combination of telithromycin and montelukast on the pharmacokinetics and pharmacodynamics of repaglinide [16].
• Although we have not observed any increase in urinary LTE(4) excretion after NKA inhalation, we have shown that pretreatment of asthmatic subjects with montelukast elicits a significant protection against NKA-induced bronchoconstriction [17].
• We measured tracheal mucus velocity, a marker of mucociliary clearance, before and for 8 hours after antigen challenge in six animals treated with montelukast (0.15 mg/kg, intravenously) 30 minutes before, 1 hour after, or 4 hours after antigen challenge [18].
• Reduction of inflammatory cell numbers in the bronchial mucosa achieved with FP plus montelukast was not significantly different from the reduction observed with FP alone in individuals with mild asthma [19].

Anatomical context of montelukast

• Treatment with budesonide and montelukast, alone and in combination, also attenuated allergen-induced sputum eosinophilia [10].
• OBJECTIVE: The purpose of this study was to evaluate the effects of leukotriene (LT) D(4) and LTE(4) and the cysLT(1) receptor antagonist montelukast on peripheral blood and bone marrow eosinophil-basophil progenitor growth and development in atopic subjects [20].
• Montelukast, but not dexamethasone, reversed the established increase in airway smooth muscle mass and subepithelial collagen deposition [11].
• Treatment with montelukast and loratadine inhibited the release of cysteinyl leukotrienes and histamine into the airways, but did not inhibit the release of columnar epithelial cells into the airways [21].
• Moreover, IL-4 and CD40-activated B lymphocytes showed an increased responsiveness to LTD(4) in terms of cytosolic calcium flux, which was totally prevented by the selective CysLT(1) antagonist montelukast [22].

Associations of montelukast with other chemical compounds

• No apparent affinity binding for the receptors was detected for the CysLT1-selective antagonists montelukast and zafirlukast [23].
• In summary, treatment of the two main components of asthma (inflammation and bronchoconstriction) with fluticasone propionate and salmeterol in a combination product was a more effective initial maintenance treatment strategy than treatment with montelukast, a single-mediator antagonist [24].
• METHODS: Ten adults with mild-to-moderate atopic asthma participated in a randomized, 4-way crossover study design comparing placebo, 5 mg of desloratadine, 10 mg of montelukast, and the combination administered at 26 hours and 2 hours before each allergen challenge conducted at least 7 days apart [25].
• Methods and Measurements: In a randomized, placebo-controlled, crossover study of 192 subjects with moderate asthma, we compared the clinical efficacy of regular treatment over 14 weeks with the combination of montelukast and salmeterol to that with the combination of beclomethasone and salmeterol in moderate asthma [26].
• Triamcinolone was better than placebo or montelukast for effects on all other surrogate inflammatory markers (P <.05), including exhaled nitric oxide, blood eosinophils, serum eosinophil cationic protein, plasma intracellular circulating adhesion molecule 1, and plasma E-selectin [27].

Gene context of montelukast

• Immature DCs and DCs matured with polyI:C, but not with LPS, responded to LTD(4) with a robust cytosolic calcium flux, which was prevented by the CysLT1 antagonist montelukast [28].
• Montelukast, an antiasthmatic drug, is a potent inhibitor of CYP2C8 in vitro [16].
• Five in vitro approaches have been used to identify the P450 isoforms responsible for the human liver microsomal oxidation of montelukast [29].
• RESULTS: Montelukast treatment induced a significant decrease of IL4 and IL13 levels (p < 0.001, for both comparisons), and a significant increase of IFN gamma (p < 0.001) [30].
• METHODS: Purified blood eosinophils were treated with or without montelukast; MK-0591, a 5-lipoxygenase-activating protein inhibitor; or leukotriene (LT) D(4) [31].

Analytical, diagnostic and therapeutic context of montelukast

• METHODS: The efficacy of montelukast alone vs montelukast-loratadine was studied in a 10-week, multicenter, randomized, double-blind, 2 x 2 crossover study [15].
• OBJECTIVE: The primary objective of this study was to determine the changes in serum levels of inflammatory mediators, clinical efficacy, and bronchial hyperresponsiveness after treatment with montelukast [32].
• METHODS: We used data from 2 clinical trials in which children with asthma received either montelukast or placebo [33].
• By immunocytochemistry, CysLT(1) receptor expression was significantly increased in airway smooth muscle cells in allergen-treated mice compared with saline-treated controls and was reduced by montelukast, but not dexamethasone, administration [11].
• BACKGROUND: Randomized controlled trials have demonstrated the efficacy of montelukast for treating asthma; whether this can be extrapolated to clinical effectiveness in routine practice has yet to be established [34].

References