Montelukast pharmacokinetics in cystic fibrosis.

Smith AL.

University of Missouri, Department of Child Health and Molecular Microbiology, Columbia, Missouri, USA.

OBJECTIVES: To determine if patients with cystic fibrosis (CF) have an altered pharmacokinetic profile of montelukast, we studied the single-dose pharmacokinetics in 12 patients with CF and 12 age- and gender-matched controls after they received a 10-mg oral dose. METHODS: Plasma samples were collected before dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours after drug administration. The specimens were analyzed by high-performance liquid chromatography (HPLC). RESULTS: The mean systemic clearance (mL/min) values (+/- SD) were not statistically different between the CF subjects (55.53 +/- 44.0 mL/min) and the controls (57.12 +/- 18.42 mL/min), nor were the results significantly different when normalized to body surface area or body weight. The mean value for elimination half-life, elimination rate constant, area under the plasma concentration versus time curve, and maximum concentration for controls was 2.37 +/- 0.38 hours, 0.30 +/- 0.05 hours(-1), 2,680.0 +/- 693.6 ng. min/mL, and 448.9 +/- 165.3 ng/mL; and for the CF patients it was 2.97 +/- 1.21 hours, 0.28 +/- 0.13 hrs(-1), 3976.1 +/- 2073.4 ng. min/mL, 606.7 +/- 237.8 ng/mL. There were no statistically significant differences (all P >.05) in the measured pharmacokinetic parameters between the CF and control subjects. CONCLUSIONS: We conclude that the dose of montelukast and the dosing interval does not need to be modified if the goal is to mimic the serum concentration used to treat asthma. The effectiveness of these concentrations for the inflammatory lung disease of patients with CF is unknown.

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Eosinophilic oesophagitis: a novel treatment using Montelukast.

Whittam J.

Department of Upper Gastro-intestinal Surgery, Hope Hospital, Salford Royal Hospitals NHS Trust, Manchester, UK.

BACKGROUND: Eosinophilic oesophagitis is a rarely diagnosed condition involving eosinophil infiltration of the oesophageal mucosa and creating significant symptoms of dysphagia. Failure to diagnose this disorder relates to reluctance to biopsy an apparently normal oesophagus. This is essential for histological diagnosis. To date, treatment success has been achieved only with corticosteroids. We describe here the use of an eosinophil stabilising agent Montelukast for the symptomatic relief of these patients. PATIENTS AND METHODS: Twelve patients have been identified with this condition in our unit since 1995, after thorough investigation of their dysphagia. We commenced eight of these patients on the leukotriene receptor antagonist Montelukast to symptomatically improve their swallowing while avoiding the use of long term corticosteroids. RESULTS: Many of these patients had been previously misdiagnosed, and therefore inappropriately and unsuccessfully treated for an extensive period prior to referral to our unit. All patients were unresponsive to acid suppression therapy alone but showed improvement in their swallowing on Montelukast. Six of eight reported complete subjective improvement, five patients remaining completely asymptomatic on a maintenance regimen. CONCLUSIONS: Eosinophilic oesophagitis is a disease that is often misdiagnosed due to lack of awareness and reluctance of clinicians to biopsy an apparently normal oesophagus in dysphagic patients, and therefore obtain a histological diagnosis. Investigation of these patients adds further evidence to this condition being a separate pathological state from gastro-oesophageal reflux and eosinophilic enteritis. Montelukast has been found to be of significant help in the symptomatic control of these patients while avoiding long term corticosteroids use.

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Fexofenadine decreases sensitivity to and montelukast improves recovery from inhaled mannitol.

Seale JP.

Department of Respiratory Medicine, PCP9, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2006, Australia.

We studied, separately, the effects of the histamine antagonist, fexofenadine hydrochloride, and the leukotriene antagonist, montelukast sodium, and their placebos on airway sensitivity to and recovery from inhaled mannitol in subjects with asthma. Two 180-mg doses of fexofenadine were taken over 14 h, and three 10-mg doses of montelukast over 36 h, with the last dose 5 h before challenge. Fexofenadine reduced sensitivity to mannitol and the PD(15) was (mean [95% confidence interval] 138 [95, 201]) mg versus placebo (51 [25, 106] mg) (p < 0.001). The final percent reduction in FEV(1) with fexofenadine was 20.8 +/- 5.4% and not different from placebo (20.1 +/- 5.3%) (p = 0.7); however, recovery was slower with fexofenadine compared with placebo (p < 0.001). By contrast, montelukast had no effect on sensitivity to mannitol and the PD(15) was 71 [36, 144] mg versus placebo (87 [51, 148] mg (p = 0.35). The total dose of mannitol delivered and the final percent reduction in FEV(1) with montelukast were 171 +/- 142 mg and 21 +/- 4% and for placebo were 182 +/- 144 mg and 20 +/- 5% (p = 0.35, p = 0.59, respectively). However, recovery of FEV(1) to baseline was faster with montelukast, with the area under the percent reduction FEV(1)-versus-time curve reduced (220 +/- 121% change.min) compared with placebo (513 +/- 182% change.min) (p < 0.001). We conclude that whereas histamine is important for the initial airway response, leukotrienes are important in sustaining the airway response to inhaled mannitol.

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Impact of montelukast on symptoms in mild-to-moderate persistent asthma and exercise-induced asthma: results of the ASTHMA survey. Adding Singulair Treatment to Handle symptoms in Mild to moderate Asthmatics.

Van den Brande P.

Department of Physiology and Pharmacology, Free University of Brussels, Boulevard du Triomphe, 1050 Brussels, Belgium. hugues.malonne ulb.ac.be

A nation-wide survey was undertaken in Belgium among general practitioners (GPs) to evaluate the impact of the leukotriene receptor antagonist (LTRA) montelukast on the control of asthma symptoms, after at least 4 weeks of treatment. Patients from 6 years of age were eligible if they were suffering from mild-to-moderate persistent asthma which was still symptomatic despite inhaled corticosteroids (ICS) treatment, or from exercise-induced asthma. Patient general satisfaction was evaluated by recording the willingness to continue the treatment. A total of 1360 GPs took part in the study and more than 11000 patients were included in the survey. Of the included patients, 85% were receiving inhaled corticosteroids, 60% of whom were also on long-acting beta2-agonists (LABA). However, despite the use of daily controller medication, 92% of the patients still reported limitation of activities, 49% difficulties with sleep and 45% early morning awakening due to asthma. Moreover, 78% of the patients used rescue medication more than twice a week. At the end of the survey, 90% of the patients expressed their willingness to continue montelukast therapy. Of the patients having symptoms at the start of the study, 87% reported amelioration in sleep while on montelukast therapy, 80% less frequent early morning awakening, 85% better ability to perform daily activities and 77% decreased need for rescue medication.

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Effectiveness of montelukast versus budesonide on quality of life and bronchial reactivity in subjects with mild-persistent asthma.

Della Vecchia R.

Respiratory Pathophysiology Center, Dept Internal Medicine, University of Chieti, School of Medicine, Chieti, Italy.

Insufficient data exist to evaluate the comparative effects of inhaled corticosteroids (ICS) versus leukotriene receptor antagonist (LTRA) on airway inflammation and quality of life (QoL). The aim of the study was to compare the effectiveness of montelukast compared to budesonide at different doses on QoL and bronchial reactivity in mild-asthmatic adult patients. 45 subjects with bronchial asthma were randomly assigned to a different treatment and divided in 3 treatment groups: A: 400 mg of budesonide twice a day; B: 10 mg of montelukast daily; C: 10 mg of montelukast daily plus 400 mg of budesonide twice a day. At the beginning of the study and at the end of the treatment period (16 weeks) all patients underwent complete clinical evaluation, pulmonary function testing and methacholine challenge test (MCHt). In group A the increase from baseline was 153.4&amp;#x0025;, in group C was 133.2&amp;#x0025;, and in group B 247.7&amp;#x0025;, the latter increase being statistically significant compared to that in the other 2 groups (p&amp;#x003C; 0.005 Wilcoxon test). In all domains the improvement in quality of life in the group treated with montelukast (group B) was significantly greater than that in the group treated with both medications (group C): in particular, the improvement was consistent in the symptoms (p&amp;#x003C; 0.01) and emotions (p&amp;#x003C; 0.01) domains, and weaker in the physical activity (p&amp;#x003C; 0.05). A similar difference was observed between group B and A, but only in the symptoms (p&amp;#x003C;0.01), emotions (p&amp;#x003C;0.01), and environmental stimuli domains (p&amp;#x003C;0.05). The personal perception of their own disease is important for a correct therapeutic management of asthma. In order to optimize the treatment, a complete adherence of the patient to the treatment itself is required, to be achieved through simplification of therapeutic schedule and easy administration of medications. Montelukast may be considered a valid alternative in the treatment of mild-persistent asthma, both for the clinical and functional benefits and for the great advantage of the once-daily dosage, which consistently improves the compliance with the chronic treatment of the disease.

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