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American Journal of Translational... 2022To compare the effects of mometasone furoate in combination with loratadine and montelukast sodium on inflammatory factors and pulmonary function in children with...
OBJECTIVE
To compare the effects of mometasone furoate in combination with loratadine and montelukast sodium on inflammatory factors and pulmonary function in children with allergic rhinitis (AR).
METHODS
In this retrospective study, a total of 89 children with AR admitted to our hospital from March 2020 to October 2021 were enrolled. Among them, 47 children who received mometasone furoate combined with loratadine were designated group A, while the other 42 with mometasone furoate combined with montelukast sodium were group B. The clinical efficacy of both groups was compared, and the levels of inflammatory factors IL-6 and TNF-α as well as the changes of pulmonary function levels were tested during the treatment. Adverse reactions during treatment were recorded. Finally, children were followed up for 3 months to record rhinitis recurrence after discontinuation of the treatment.
RESULTS
There was no statistical difference in clinical treatment efficacy between both groups (P>0.05), while the levels of IL-6, TNF-α, and IgE were lower in children in group A than in group B at 2 weeks of treatment. Group A's lung function indexes, including forced expiratory volume in one second (FEV1%), forced expiratory volume in one second/forced vital capacity (FEV1/FVC) and peak expiratory flow (PEF), were higher than in group B (all P<0.05). The total incidence of adverse reactions was dramatically lower in group A than group B (P<0.05). Follow-up demonstrated no difference in the recurrence rate of rhinitis between both groups of children (P>0.05). Higher TNF-α after treatment, history of allergy, family history of rhinitis, combined asthma, and parental history of smoking were independent risk factors for relapse after discontinuation of the drug in children.
CONCLUSION
Both mometasone furoate combined with either loratadine or montelukast sodium had good effects in AR, while the first option had a faster inhibitory effect on inflammatory factors and a better protection of lung function in children.
PubMed: 36398245
DOI: No ID Found -
Biopharmaceutics & Drug Disposition Dec 1997A study was conducted to (i) characterize the multiple-dose pharmacokinetics of oral montelukast sodium (MK-0476), 10 mg d-1 in healthy young subjects (N = 12), (ii)... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A study was conducted to (i) characterize the multiple-dose pharmacokinetics of oral montelukast sodium (MK-0476), 10 mg d-1 in healthy young subjects (N = 12), (ii) evaluate the pharmacokinetics of montelukast in healthy elderly subjects (N = 12), and (iii) compare the pharmacokinetics and oral bioavailability of montelukast between elderly and young subjects. Following oral administration of montelukast sodium, 10 mg d-1 (the therapeutic regimen for montelukast sodium) for 7 d, there was little difference in the plasma concentration-time profiles of montelukast in young subjects between day 1 and day 7 dosing. On average, trough plasma concentrations of montelukast were nearly constant, ranging from 18 to 24 ng mL-1 on days 3-7, indicating that the steady state of montelukast was attained on day 2. The mean accumulation ratio was 1.14, indicating that this dose regimen results in a 14% accumulation of montelukast. In elderly subjects, mean values of plasma clearance (Cl), steady-state volume of distribution (Vss), plasma terminal half-life (t1/2), and mean residence time in the body (MRTIV) following a 7 mg intravenous (5 min infusion) administration of montelukast sodium in the elderly were 30.8 mL min-1, 9.7 L, 6.7 h, and 5.4 h, respectively. Following a 10 mg oral dose, the bioavailability of montelukast in healthy elderly averaged 61%, very close to that (62%) determined previously in healthy young subjects. Also following the 10 mg oral administration, the mean values of AUC0-->infinity, Cmax, tmax, and t1/2, and the mean plasma concentration-time profile of montelukast in the elderly, were generally similar to those in young subjects, indicating that age has little or no effect on the pharmacokinetics of montelukast. There is no need to modify dosage as a function of age.
Topics: Acetates; Administration, Oral; Adult; Age Factors; Aged; Area Under Curve; Biological Availability; Chromatography, High Pressure Liquid; Cyclopropanes; Female; Half-Life; Humans; Male; Middle Aged; Quinolines; Sulfides
PubMed: 9429741
DOI: 10.1002/(sici)1099-081x(199712)18:9<769::aid-bdd60>3.0.co;2-k -
Clinical Pediatrics 2004This study tests the hypothesis that montelukast sodium, a selective leukotriene receptor antagonist, will decrease the duration of the effusion of otitis media.... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
This study tests the hypothesis that montelukast sodium, a selective leukotriene receptor antagonist, will decrease the duration of the effusion of otitis media. Tympanometry and spectral gradient acoustic reflectometry were used to confirm the effusion of otitis media in patients between 2 and 12 years of age. Patients were treated with amoxicillin for 10 days and montelukast sodium or placebo for 30 days in a random, double-blind manner. Sixty patients completed the study: 31 received placebo and 29 received montelukast sodium. At a 4-week follow-up visit, 5 ears (16%) were free of effusion in the placebo group and 17 (58%) in the montelukast sodium group. The difference was significant. The efficacy of montelukast sodium in clearing the effusion was 49%.
Topics: Acetates; Child; Child, Preschool; Cyclopropanes; Double-Blind Method; Female; Humans; Leukotriene Antagonists; Male; Otitis Media with Effusion; Placebos; Quinolines; Sulfides; Treatment Outcome
PubMed: 15248005
DOI: 10.1177/000992280404300604 -
Pharmaceutical Research Mar 1996The safety, tolerability, and pharmacokinetics of intravenous *i.v.) montelukast sodium (Singulair, MK-0476), and the oral bioavailability of montelukast sodium in... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
PURPOSE
The safety, tolerability, and pharmacokinetics of intravenous *i.v.) montelukast sodium (Singulair, MK-0476), and the oral bioavailability of montelukast sodium in healthy males and healthy females were studied.
METHODS
This was a two-part study. Part I was a four-period study in males of rising i.v. doses of montelukast sodium (3, 9, and 18 mg) administered as 15-minute constant-rate i.v. infusions (Periods 1-3), followed by a 10-mg oral tablet dose of montelukast sodium (Period 4) under fasting conditions. Part II was a four-period study in females of i.v. montelukast sodium (9 mg) infused over 15 and 5 minutes (Periods 5 and 6, respectively) or injected as a bolus over 2 minutes (Period 7), followed by a 10-mg oral tablet dose of montelukast sodium (Period 8). Plasma samples were collected and analyzed by HPLC.
RESULTS
In males (N = 6), as the i.v. dose of montelukast sodium increased from 3 to 18 mg, the area under the plasma concentration-time curve of montelukast sodium from time 0 to infinity (AUC) increased proportionately. The mean values of plasma clearance (CL), steady-state volume of distribution (Vss), plasma terminal half-life (t1/12), and mean residence time in the body (MRTi.v.) of montelukast sodium were 45.5 ml/min, 10.5 1, 5.1 hr, and 3.9 hr, respectively, and remained essentially constant over the i.v. dosage range. Following oral administration of a 10-mg tablet of montelukast sodium, the AUC, maximum plasma concentration (Cmax), time when Cmax occurred (Tmax), apparent t1/12, mean absorption time (MAT), and bioavailability (F) of montelukast sodium averaged 2441 ng.hr/ml, 385 ng/ml. 3.7 hr, 4.9 hr, 3.4 hr, and 66%, respectively. Following i.v. administration of 9 mg of montelukast sodium to females (N = 6), the values of CL, Vss, t1/2, and MRT i.v. averaged 47.6 ml/min, 9.6 1, 4.5 hr, and 3.6 hr, respectively. Following oral administration of a 10-mg tablet to females, the mean AUC, Cmax, Tmax, apparent t1/2, MAT and F were 2270 ng.hr/ml, 350 ng/ml, 3.3 hr, 4.4 hr, 2.6 hr, and 58%, respectively. These parameter values were similar to or slightly smaller than those in healthy males receiving the same i.v. and oral doses.
CONCLUSIONS
The disposition kinetics of montelukast sodium were linear. Gender had little or no effect on the kinetics of montelukast sodium. Safety results from this study indicate that intravenous doses of montelukast sodium from 3 to 18 mg and a 10-mg oral dose are well tolerated.
Topics: Acetates; Administration, Oral; Adult; Cyclopropanes; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Injections, Intravenous; Leukotriene Antagonists; Male; Membrane Proteins; Placebos; Quinolines; Receptors, Leukotriene; Sex Factors; Sulfides
PubMed: 8692739
DOI: 10.1023/a:1016056912698 -
BMJ (Clinical Research Ed.) Mar 2022
Topics: Acetates; Cyclopropanes; Humans; Quinolines; Sulfides
PubMed: 35351683
DOI: 10.1136/bmj-2021-067554 -
Biomedical Chromatography : BMC Apr 2022Montelukast sodium (MLS) is a leukotriene receptor antagonist drug used in the treatment of asthma, bronchospasm, allergic rhinitis and urticaria. A reversed-phase high...
Montelukast sodium (MLS) is a leukotriene receptor antagonist drug used in the treatment of asthma, bronchospasm, allergic rhinitis and urticaria. A reversed-phase high performance liquid chromatography method was developed to separate, identify and quantitative determination of MLS and its eight known organic impurities in tablet dosage form using a C column and mobile phases consisting of a gradient mixture of pH 2.5 phosphate buffer and acetonitrile. The stability-indicating character of the developed method was proven using stress testing (1 m HCl at 80°C/30 min, 1 m NaOH at 80°C/30 min, H O at 80°C/30 min, 3% H O at 25°C/1 min, dry heat at 105°C/10 h and UV-vis light/4 days) and was validated for specificity, quantitation limit, linearity, precision, accuracy and robustness. For MLS and its eight known impurities, the quantitation limits, linearity and recoveries were 0.015-0.03 μg/ml, correlation coefficient > 0.997 (R > 0.995) and 85.5-107.0%, respectively. The developed chromatographic method is suitable for impurity profiling and also for assay determination of MLS in bulk drugs and pharmaceutical formulations. The mass values (m/z) of newly formed degradation products (DP1 and DP2) of montelukast sodium were identified using liquid chromatography-mass spectrometry.
Topics: Acetates; Chromatography, High Pressure Liquid; Chromatography, Liquid; Cyclopropanes; Drug Stability; Quinolines; Reproducibility of Results; Sulfides; Tablets
PubMed: 34994006
DOI: 10.1002/bmc.5330 -
Medicine May 2017This study was designed to investigate the clinical effect of montelukast sodium combined with inhaled corticosteroids in the treatment of children with obstructive... (Observational Study)
Observational Study Randomized Controlled Trial
This study was designed to investigate the clinical effect of montelukast sodium combined with inhaled corticosteroids in the treatment of children with obstructive sleep apnea syndrome (OSAS).One hundred ninety-five children were enrolled and divided into 3 groups: groups A, B, and C; the group A (oral use of montelukast sodium), group B (nasal spray of mometasone furoate), and group C (oral use of montelukast sodium + nasal spray of mometasone furoate). Telephone questionnaire surveys were carried out. Polysomnography monitoring was performed and lateral x-ray radiographs of the cervical spine were taken before treatment and at 12 weeks after treatment. The improvement of clinical symptoms after treatment and its effective rate were analyzed. The difference in clinical characteristics between groups C1 and C2 was analyzed.In the 3 groups, clinical symptoms improved at 12 weeks after treatment compared with before (P < .05 or P < .01). Apnea-hypopnea index value decreased (P < .05) and minimal SaO2 increased (P < .05), while adenoidal/nasopharyngeal ratio was reduced (P < .05). Compared with groups A and B, group C had a shortened response duration of snoring, apnea, and restless sleep (P < .05). Differences in the response duration of buccal respiration and hyperhidrosis were not statistically significant (P > .05). The total effective rate was higher in group C than in A and B (P < .05), while the differences in all indices between groups A and B were not statistically significant (P > .05). The difference in the grade of the size of the tonsil between groups C1 and C2 was statistically significant (P < .05).The total effective rate of the combined treatment was higher than that of the single use of any of the 2 drugs, which allowed the rapid relief of symptoms. Drug treatment may have a poor curative effect in the treatment of OSAS patients with ≥ grade 3 tonsil hypertrophy.
Topics: Acetates; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Cervical Vertebrae; Child, Preschool; Cyclopropanes; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Mometasone Furoate; Nasal Sprays; Polysomnography; Quinolines; Respiratory System Agents; Sleep Apnea, Obstructive; Sulfides; Surveys and Questionnaires; Treatment Outcome
PubMed: 28489737
DOI: 10.1097/MD.0000000000006628 -
Life Sciences Jul 2023Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast...
Montelukast prevents mice against carbon tetrachloride- and methionine-choline deficient diet-induced liver fibrosis: Reducing hepatic stellate cell activation and inflammation.
AIMS
Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (CysLTR1) that protects against inflammation and oxidative stress. However, the function of montelukast in liver fibrosis remains unknown. In this study, we examined whether the pharmacological inhibition of CysLTR1 could protect mice against hepatic fibrosis.
MATERIALS AND METHODS
Carbon tetrachloride (CCl) and methionine-choline deficient (MCD) diet models were used in this study. The expression of CysLTR1 in liver were detected by RT-qPCR and Western blot analysis. Liver hydroxyproline levels, fibrotic genes expression, serum biochemical indexes and inflammatory factors were used to evaluate the effect of montelukast on liver fibrosis, injury, and inflammation. In vitro, we used the RT-qPCR and Western blot analysis to assess CysLTR1 in mouse primary hepatic stellate cell (HSC) and human LX-2 cell line. The role of montelukast on HSC activation and the underlying mechaisms were determined using RT-qPCR analysis, Western blot and immunostaining assays.
KEY FINDINGS
Chronic stimulation from CCl and MCD diet upregulated the mRNA and protein levels of CysLTR1 in the liver. Pharmacological inhibition of CysLTR1 by montelukast ameliorated liver inflammation and fibrosis in both models. Mechanistically, montelukast suppressed HSC activation by targeting the TGFβ/Smad pathway in vitro. The hepatoprotective effect of montelukast was also associated with reduced liver injury and inflammation.
SIGNIFICANCE
Montelukast suppressed CCl- and MCD-induced chronic hepatic inflammation and liver fibrosis. CysLTR1 might be a therapeutic target for treating liver fibrosis.
Topics: Mice; Humans; Animals; Carbon Tetrachloride; Methionine; Hepatic Stellate Cells; Signal Transduction; Liver Cirrhosis; Liver; Fibrosis; Racemethionine; Inflammation; Diet; Transforming Growth Factor beta1
PubMed: 37178864
DOI: 10.1016/j.lfs.2023.121772 -
Allergy and Asthma Proceedings 2014It has proven efficacy in reducing asthma exacerbations, but the effect size of montelukast (a leukotriene receptor antagonist) for varied severity of asthma... (Meta-Analysis)
Meta-Analysis Review
It has proven efficacy in reducing asthma exacerbations, but the effect size of montelukast (a leukotriene receptor antagonist) for varied severity of asthma exacerbations is not systematically assessed. This study was designed to systematically explore the evidence for montelukast, as first-line or add-on therapy, in preventing and treating asthma exacerbations in adult patients with asthma. Randomized controlled trials were searched in PubMed, CENTRAL, Web of Science, Embase, and OVID up to March 2013, where montelukast prevented or treated asthma exacerbations in adults. Primary outcomes were the number of patients experiencing exacerbations in chronic asthma and hospitalizations in acute asthma. Odds ratio (OR) with 95% confidence intervals (CI), risk difference, and number needed to treat (NNT) were calculated and pooled. Adverse events were also assessed in chronic asthma. Twenty trials for chronic asthma and six for acute asthma were identified. In comparison with placebo, adults with chronic asthma receiving montelukast had significantly reduced number of exacerbations (OR = 0.60 and 95% CI, 0.49, 0.74; NNT = 17 and 95% CI, 12, 29). However, montelukast was inferior to inhaled corticosteroids (ICSs) (OR = 1.63; 95% CI, 1.29, 2.0) and ICS plus long-acting beta2-agonist (LABA; OR = 3.94; 95% CI, 1.64, 9.48) as the first-line therapies and LABA (OR = 1.22; 95% CI, 1.05, 1.42) as the add-on therapies in reducing asthma exacerbations. In acute asthma, montelukast could statistically improve peak expiratory flow percent predicted (p = 0.008) and reduce systemic corticosteroid intake (p = 0.005). Montelukast had low risk in hoarseness and insomnia. Our meta-analysis suggests that montelukast significantly reduces mild, moderate, and part of severe exacerbations in chronic mild to moderate asthma, but it has inferior efficacy to ICS or ICS plus LABA.
Topics: Acetates; Anti-Asthmatic Agents; Asthma; Clinical Trials as Topic; Cyclopropanes; Disease Progression; Humans; Leukotriene Antagonists; Quinolines; Sulfides; Treatment Outcome
PubMed: 24992547
DOI: 10.2500/aap.2014.35.3745 -
American Journal of Rhinology & Allergy 2011Nitric oxide (NO) imbalance appears to be important in the pathogenesis of allergic rhinitis. NO is synthesized from l-arginine by NO synthase (NOS). Competing with NOS...
BACKGROUND
Nitric oxide (NO) imbalance appears to be important in the pathogenesis of allergic rhinitis. NO is synthesized from l-arginine by NO synthase (NOS). Competing with NOS for l-arginine is arginase, which catalyzes the hydrolysis of arginine to urea and ornithine. Therefore, increased serum arginase activity could potentially limit NO production catalyzed by inducible NOS, thus contributing to allergic rhinitis. This study was designed to investigate the effect of the cysteinyl leukotriene type 1 receptor antagonist, montelukast sodium on serum arginase levels in patients with seasonal allergic rhinitis.
METHODS
Twenty-five patients with seasonal allergic rhinitis (SAR; treatment group) and 16 nonasthmatic patients without allergic rhinitis (control group) were included in the study. Serum arginase levels and the mean total nasal symptoms scores were measured before and after oral montelukast sodium (10 mg) was administered daily for 4 weeks to the treatment group.
RESULTS
Serum arginase levels and the mean total nasal symptoms scores were significantly lower in the treatment group after montelukast sodium administration compared with the baseline levels (p = 0.001). Serum arginase levels were significantly lower in the treatment group compared with the control group (p = 0.01). There was no statistically significant difference between the serum arginase levels of the treatment group before treatment and the control group (p = 0.05). There was a weak correlation between the mean total nasal symptoms scores and serum arginase levels in the treatment group before montelukast sodium administration (rs = 0.40; p = 0.05).
CONCLUSION
Montelukast sodium may reduce serum arginase levels and total nasal symptoms scores of patients with SAR. Additional studies that compare the effectiveness of nasal corticosteroid and montelukast sodium on serum arginase levels should be conducted.
Topics: Acetates; Administration, Oral; Adult; Allergens; Arginase; Cyclopropanes; Female; Humans; Leukotriene Antagonists; Male; Middle Aged; Oxidative Stress; Poaceae; Pollen; Quinolines; Rhinitis, Allergic, Seasonal; Sulfides; Trees
PubMed: 21439134
DOI: 10.2500/ajra.2011.25.3626