• Clinical and Experimental Pediatrics
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• v.52 no.2
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• pp.181-186
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• 2009

Purpose : Inflammation plays a potential role in the pathogenesis of bronchopulmonary dysplasia (BPD). Strategies for preventing BPD include respiratory management, antioxidants, nutritional treatment, and others such as anti-inflammatory agents. We aimed to assess the safety, tolerability, and efficacy of montelukast (MK), a cysteinyl leukotriene 1 receptor antagonist, as an add-on therapy in BPD. Methods : In addition to currently available standard measures such as oxygen supplementation, bronchodilators, nutritional support, and/or diuretics, montelukast was administered to 15 preterm infants with BPD. MK was given orally (1 mg/kg/d) for a mean period of 12 weeks. We compared safety and efficacy parameters with historical controls. Results : All 15 patients survived, and no differences were found in the incidence of adverse reactions between the 2 groups. The ventilation index was significantly improved after 2 weeks in MK group compared with historical controls. There were no significant differences in other respiratory parameters (MAP, oxygen dependency, and ventilator dependency) between the groups, but the MK group showed trends of greater improvement. Conclusion : Administration of MK 1 mg/kg/d was well tolerated in preterm BPD patients as an add-on therapy. We demonstrated that after 2 weeks of MK administration of 1 mg/kg/d, MK had beneficial therapeutic effects on BPD patients as an add-on to the standard therapy. Further multicenter randomized controlled clinical trials are needed to confirm the efficacy and safety of MK as a useful supplement to standard therapy for BPD patients.

• Journal of Pharmaceutical Investigation
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• v.41 no.5
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• pp.289-294
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• 2011

A rapid and specific high performance liquid chromatography-tandem mass (LC/MS/MS) method for the analysis of montelukast in human plasma has been developed and validated. After cold acetonitrile-induced precipitation of the plasma samples, montelukast and glipizide (internal standard, IS) were eluted on a reverse-phase $C_{18}$ column by isocratic mobile phase consisted of 10 mM ammonium formate buffer (adjusted to pH 3.5 with formic acid) and acetonitrile (3:97, v/v). Acquisition was performed with multiple reaction monitoring (MRM) mode by monitoring the transitions: m/z 587.2${\rightarrow}$ 423.2 for montelukast and m/z 446.0${\rightarrow}$321.2 for IS. Ranges of concentration for calibration curves (10-1000 ng/mL) showed correlation coefficients ($r^2$) were better than 0.9948. Precision of intra- and inter-day ranged from 3.70 to 11.68% and from 3.04 to 12.95%, accuracy of intra-day and inter-day ranged from 93.34 to 102.75% and from 100.79 to 107.63%, respectively. The described method provides a fast and sensitive analytical tool for determining montelukast levels in plasma, and was successfully applied to a pharmacokinetic study in 16 healthy human subjects after oral administration of 10mg tablet formulation of montelukast sodium under fasting conditions.

• Clinical and Experimental Pediatrics
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• v.48 no.7
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• pp.766-771
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• 2005

Purpose : Cysteinyl leukotrienes are important inflammatory mediators in the pathogenesis of asthma; therefore interruption of cysteinyl leukotrienes by leukotriene receptor antagonists improves clinical symptoms in the management of patients with mild to moderate asthma. We evaluated whether clinical response to montelukast, a leukotriene receptor antagonist, in childhood asthma was predicted by genotypes of leukotriene $C_4$ synthase($LTC_4S$) promoter gene polymorphism. Methods : An 8-week prospective, open trial of montelukast was carried out in 161 children with mild to moderate asthma. Genotyping of $LTC_4S$ gene polymorphism was determined by restriction fragment length polymorphism. Results : The distribution of the $LTC_4S$ genotypes AA, AC, and CC was 70.8 percent, 23.6 percent, and 5.6 percent, respectively in asthma group and 74.0 percent, 22.6 percent, and 3.4 percent, respectively in control group. A statistically significant difference in the distribution of $LTC_4S$ genotype was not observed between the asthma and the control groups, and there was no significant difference between the $LTC_4S$ genotype and asthma severity. The responders to montelukast were significantly prevalent in the mild asthma group(P<0.05). There was no significant difference in the distribution of the responders compared to non-responders within genotype in the total asthma group or the moderate asthma group. However, the responsiveness for montelukast was significant difference within genotype for both AA and AC/CC in the mild asthma group : The AA genotype was more included in the responder group(P<0.05). Conclusion : In the mild persistent asthma group, the A allele of $LTC_4S$ polymorphism may be regarded as a predictable factor for clinical response to montelukast. However, LTC4S polymorphism was not significantly associated with the clinical response to montelukast in asthmatic children.

• Tuberculosis and Respiratory Diseases
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• v.63 no.4
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• pp.337-345
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• 2007

Backgrounds: Although glucocorticoids are one of the most potent anti-inflammatory agents, they have limited effect on cysteinyl leukotriene biosynthesis. In addition, the response to inhaled corticosteroids (ICS) and inhaled long-acting ${\beta}_2-agonists$ (LABA) combination therapy in moderate to severe persistent asthmatics varies. Additional therapy with leukotriene receptor antagonists (LTRA) in patients with moderate to severe asthma suboptimally controlled with ICS and LABA combination therapy would be complementary to asthma control. Methods: One hundred and ninety eight asthmatics entered a 2 month, open-label descriptive study. Patients suffering from persistent asthma and suboptimally controlled on a combination therapy of fluticasone/salmeterol or budesonide/formoterol were given montelukast 10 mg daily as an add-on therapy. The level of asthma control was assessed using the Asthma Control Questionnaire (ACQ) including $FEV_1%$ predicted at the baseline and after a 2-month treatment with montelukast. A global evaluation of the treatment was also made by the patients and physicians. Results: The mean ACQ score decreased significantly on montelukast ($11.5{\pm}5.4$ at baseline vs. $6.7{\pm}5.0$), with a significant improvement in all individual symptom scores (p<0.01). The $FEV_1%$ predicted values did not show any significant change. 59.9% of patients and 59.4% of physicians reported global improvement in their asthma (${\kappa}=0.85$). Conclusion: These results suggest that the addition of montelukast in patients with persistent asthma that is suboptimally contolled by combination therapy of ICS and LABA might confer complementary effects on asthma control.

• Allergy, Asthma & Immunology Research
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• v.10 no.6
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• pp.686-697
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• 2018

Purpose: Several markers for eosinophilic inflammation have been proposed to predict response to asthma treatment. However, definitive criteria for treatment decisions have not yet been established. We investigate a potentially useful relatively non-invasive biomarker, eosinophil-derived neurotoxin (EDN), to predict favorable responses to budesonide or montelukast, common treatment for children with asthma. Methods: Young children (1 to 6 years old) were enrolled in this randomized, parallel, 2-group, open-label trial. Criteria for eligibility included: 1) being symptomatic during the run-in period; and 2) having a serum EDN (sEDN) level ${\geq}53ng/mL$, with positive specific immunoglobulin E to house dust mite. Eligible patients were randomly placed into 2 groups: the BIS group received budesonide inhalation suspension (BIS) 0.5 mg once daily; the MONT group received montelukast 4 mg once daily. Ineligible patients were invited to receive montelukast 4 mg once daily (OBS group). Treatment period was 12 weeks. Results: Asthma control days increased significantly in the BIS and MONT groups (P < 0.000) over the 12-week study period. There was no significant change in sEDN in the BIS group but there was a significant decrease in the MONT group (P < 0.000). Patients in the OBS group with high EDN levels (> 53 ng/mL) showed a significant decrease due to MONT treatment (P = 0.023). Rescue medication usage significantly decreased in the BIS and MONT groups (P < 0.000). Conclusions: EDN is a useful relatively non-invasive biomarker for predicting responses to montelukast and budesonide treatment of preschool children with beta2-agonist responsive recurrent wheeze and multiple-trigger wheeze (Trial registry at UMIN Clinical Trials Registry, UMIN000008335).

• Clinical and Experimental Pediatrics
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• v.58 no.9
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• pp.347-353
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• 2015

Purpose: The purpose of this study was to evaluate the efficacy and safety of Montelukast sodium in the prevention of bronchopulmonarydysplasia (BPD). Methods: The Interventional study was designed as a multicenter, prospective, and randomized trial, with open labeled and parallel-experimental groups, 66 infants were enrolled and allocated to either the case group (n=30) or the control group (n=36) based on gestational age (GA). Infants in the case group were given Montelukast sodium (Singulair) based on their body weight (BW). Zero week was defined as the start time of the study. Results: The incidence of moderate to severe BPD was not different between the groups (case group: 13 of 30 [43.3%] vs. control group: 19 of 36 [52.8%], P=0.912). Additionally, secondary outcomes such as ventilation index, mean airway pressure and resort to systemic steroids were not significantly different. There were no serious adverse drug reactions in either group, and furthermore the rate of occurrence of mild drug related-events were not significantly different (case group: 10 of 42 [23.8%] vs. control group: 6 of 48 (15.8%), P=0.414). Conclusion: Montelukast was not effective in reducing moderate or severe BPD. There were no significant adverse drug events associated with Montelukast treatment.

• Mass Spectrometry Letters
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• v.11 no.4
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• pp.71-76
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• 2020

While montelukast (ML), a cysteinyl-leukotriene type 1 receptor (CysLT1) antagonist is widely used to treat symptoms of rhinitis or asthma, its formulations are mainly limited to solid preparation due to its instability. Recently, there have been attempts to develop various ML dosage forms, and this situation increases the demand of sensitive and creditable methods to determine ML in various samples such as plasma. Thus, here, a simple and efficient method to determine ML in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was presented. The mixture of DCM:EtOAc (25:75, v/v), the optimized extract solvent for LLE was found to be effective to extract ML without hydrophilic salts and proteins from the sample with limited volume. Also, the use of zafirlukast, instead of expensive ML-d6, as the internal standard makes the present method economical. The developed method was successfully validated in terms of selectivity, matrix effects (-14.8--6.9%), linearity (r230.998 within 0.5-500 ng/mL), sensitivity (the limit of detection and the lower limit of quantitation, ≤0.5 ng/mL), accuracy (88.4-100.6%), precision (3.0-13.3%), and recovery (80.8-86.3%) by following the FDA guidelines. Finally, the applicability of the validated method to pharmacokinetics (PK) studies was confirmed by the successful determination of PK parameters through it following oral administration of Singulair® granule in rats. Therefore, the present method can contribute to the development of new ML formulations through its performance to determine ML in rat plasma efficiently and sensitively.

• Journal of Integrative Natural Science
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• v.9 no.4
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• pp.228-233
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• 2016

Cysteinyl leukotrienes are inflammatory mediators having important role in pathophysiological conditions such as asthma and allergic rhinitis. CysLT1 receptor mediates most of the disease regulatory actions of the CysLTs and it is been implicated in a number of inflammatory conditions including gastrointestinal and cardiovascular diseases. Hence in the present study, molecular docking of CysLT1 was performed with its potent and orally efficacious antagonist CP-199330 and CP-199331. The aim of this study was to compare the interaction of CP-199330 and CP-199331 with known drugs such as Zafirlukast, Pranlukast and Montelukast which had already showed clinical efficacy in the treatment of asthma. The residues such as TYR83, GLN274, LYS311 and SER313 were found to interact with both the antagonist and the known drugs. Also, we noticed the docking scores and interaction of the antagonists were comparable with the known drugs. Hence these antagonists could serve as better drugs for the treatment of allergy.

• Korean Journal of Clinical Pharmacy
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• v.24 no.1
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• pp.26-32
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• 2014

Purpose: The aim of this study was to investigate drug prescription patterns for the treatment of asthma and chronic obstructive pulmonary disease (COPD) patients in Korea. Methods: Ambulatory adult patients who were diagnosed and received treatment for the asthma (ICD-10 code J45) or COPD (ICD-10 code J44) from January 2009 to September 2011 in two independent secondary hospitals in Korea were enrolled in this study. Prescribed drug lists were generated based on the evidence-based guidelines and prescribed drug dosage forms were identified from the patient medical records and computerized drug prescription databases of the study centers. Results: Total numbers of asthma and COPD patient enrolled in this study were 2,432 and 2,615, respectively. Individual prescription-based accumulated numbers of patient were 12,021 for asthma and 16,584 for COPD. The most commonly prescribed three drugs were oral predisolone, oral formoterol and oral montelukast for asthma and oral formoterol, oral doxofylline and inhaled tiotropium for COPD. Frequencies of oral drugs were 83.4% and 63.3% while inhalers were 16.4% and 30.2%, for asthma and COPD, respectively. Conclusion: The oral treatment was prescribed more in asthma and COPD patients than inhalers. To enhance the compliance of evidence-based guidelines for these chronic airway diseases, more realistic and specific strategies to increase the use of inhalers recommended as primary treatment options for asthma and COPD would be required.