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The Journal of Asthma : Official... Nov 2023Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics...
Efficacy and safety of fixed-dose combination of Bilastine-Montelukast in adult patients with allergic rhinitis: a phase III, randomized, multi-center, double-blind, active controlled clinical study.
BACKGROUND
Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics (Levocetirizine) and highly selective leukotriene receptor antagonist (LTA) (Montelukast) combination have shown additive benefits and are widely prescribed for AR.
OBJECTIVE
Evaluate the efficacy and safety of Bilastine 20 mg and Montelukast 10 mg fixed-dose combination (FDC) therapy in patients with AR.
METHODS
A randomized, double-blind, comparative, parallel, phase III study was conducted to evaluate efficacy and safety of Bilastine 20 mg and Montelukast 10 mg FDC at 16 tertiary care otolaryngology centres in India. Adult patients with AR for one year with IgE antibody positive and 12-h NSS score >36 in 3 days were randomized to receive either Bilastine 20 mg and Montelukast 10 mg or Montelukast 10 mg & Levocetirizine 5 mg tablets for 4 weeks. The change in total symptom score (nasal symptom scores (NSS) & non-nasal symptom scores (NNSS)) from baseline to week 4 was assessed as primary endpoint. Secondary endpoints included changes in TSS, NSS, NNSS, individual symptom scores (ISS), Rhinoconjunctivitis Quality of Life (RQLQ), discomfort due to rhinitis (VAS), and clinical global impression (CGI) scores.
RESULTS
The change in mean TSS from baseline to week 4 in Test group (16.6 units) was comparable to reference group (17 units) (= 0.8876). The difference in change in mean NSS, NNSS and ISS from baseline to day 7, 14, 28 were comparable. RQLQ improved from baseline to Day 28. Significant improvements were observed in discomfort due to AR measured by VAS and CGI scores from baseline to day 14 and 28. The safety and tolerability of patients were comparable between the groups. All adverse events (AEs) were mild to moderate in severity. No patient discontinued due to AEs.
CONCLUSIONS
The FDC of Bilastine 20 mg and Montelukast 10 mg was efficacious and well tolerated in Indian patients with AR.
PubMed: 37140964
DOI: 10.1080/02770903.2023.2209175 -
Journal of Applied Microbiology May 2024Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established...
AIMS
Drug repurposing is an attractive strategy to control biofilm-related infectious diseases. In this study, two drugs (montelukast and cefoperazone) with well-established therapeutic applications were tested on Pseudomonas aeruginosa quorum sensing (QS) inhibition and biofilm control.
METHODS AND RESULTS
The activity of montelukast and cefoperazone was evaluated for Pqs signal inhibition, pyocyanin synthesis, and prevention and eradication of Ps. aeruginosa biofilms. Cefoperazone inhibited the Pqs system by hindering the production of the autoinducer molecules 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (the Pseudomonas quinolone signal or PQS), corroborating in silico results. Pseudomonas aeruginosa pyocyanin production was reduced by 50%. The combination of the antibiotics cefoperazone and ciprofloxacin was synergistic for Ps. aeruginosa biofilm control. On the other hand, montelukast had no relevant effects on the inhibition of the Pqs system and against Ps. aeruginosa biofilm.
CONCLUSION
This study provides for the first time strong evidence that cefoperazone interacts with the Pqs system, hindering the formation of the autoinducer molecules HHQ and PQS, reducing Ps. aeruginosa pathogenicity and virulence. Cefoperazone demonstrated a potential to be used in combination with less effective antibiotics (e.g. ciprofloxacin) to potentiate the biofilm control action.
Topics: Pseudomonas aeruginosa; Biofilms; Sulfides; Quorum Sensing; Anti-Bacterial Agents; Acetates; Quinolines; Cyclopropanes; Cefoperazone; Microbial Sensitivity Tests; Pyocyanine; Ciprofloxacin; Quinolones
PubMed: 38587815
DOI: 10.1093/jambio/lxae088 -
Molecular Medicine Reports Aug 2024Montelukast and zafirlukast, cysteinyl leukotriene receptor antagonists (LTRAs), trigger apoptosis and inhibit cell proliferation of triple‑negative breast cancer...
Differential effects of montelukast and zafirlukast on MDA‑MB‑231 triple‑negative breast cancer cells: Cell cycle regulation, apoptosis, autophagy, DNA damage and endoplasmic reticulum stress.
Montelukast and zafirlukast, cysteinyl leukotriene receptor antagonists (LTRAs), trigger apoptosis and inhibit cell proliferation of triple‑negative breast cancer MDA‑MB‑231 cells. By contrast, only zafirlukast induces G/G cell cycle arrest. The present study compared the effects of these drugs on proteins regulating cell proliferation, apoptosis, autophagy, and endoplasmic reticulum (ER) and oxidative stress using reverse transcription‑quantitative PCR, western blotting and flow cytometry. The expression of proliferating markers, Ki‑67 and proliferating cell nuclear antigen, was decreased by both drugs. Zafirlukast, but not montelukast, decreased the expression of cyclin D1 and CDK4, disrupting progression from G to S phase. Zafirlukast also increased the expression of p27, a cell cycle inhibitor. Both drugs decreased the expression of anti‑apoptotic protein Bcl‑2 and ERK1/2 phosphorylation, and increased levels of the autophagy marker LC3‑II and DNA damage markers, including cleaved PARP‑1, phosphorylated (p)‑ATM and p‑histone H2AX. The number of caspase 3/7‑positive cells was greater in montelukast‑treated cells compared with zafirlukast‑treated cells. Montelukast induced higher levels of the ER stress marker CHOP compared with zafirlukast. Montelukast activated PERK, activating transcription factor 6 (ATF6) and inositol‑requiring enzyme type 1 (IRE1) pathways, while zafirlukast only stimulated ATF6 and IRE1 pathways. GSK2606414, a PERK inhibitor, decreased apoptosis mediated by montelukast, but did not affect zafirlukast‑induced cell death. The knockdown of CHOP by small interfering RNA reduced apoptosis triggered by montelukast and zafirlukast. In conclusion, the effects on cell cycle regulator proteins may contribute to cell cycle arrest caused by zafirlukast. The greater apoptotic effects of montelukast may be caused by the higher levels of activated caspase enzymes and the activation of three pathways of ER stress: PERK, ATF6, and IRE1.
Topics: Humans; Sulfides; Cyclopropanes; Quinolines; Apoptosis; Acetates; Endoplasmic Reticulum Stress; Cell Line, Tumor; Autophagy; Sulfonamides; Indoles; Female; DNA Damage; Phenylcarbamates; Tosyl Compounds; Cell Proliferation; eIF-2 Kinase; Endoribonucleases; Cell Cycle Checkpoints; Transcription Factor CHOP; Cell Cycle; Leukotriene Antagonists; Protein Serine-Threonine Kinases
PubMed: 38904207
DOI: 10.3892/mmr.2024.13265 -
Survey of Ophthalmology 2024Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and... (Review)
Review
Vernal keratoconjunctivitis (VKC) is a chronic, progressive, and potentially sight-threatening form of ocular inflammatory disease that primarily affects children and young adults. Prevalence varies by region, ranging from <2 per 10,000 in the United States to as high as 1,100 per 10,000 in parts of Africa. The rarity of VKC in developed countries can make differential diagnosis challenging, and treatment is often delayed until the disease is advanced, and symptoms are significantly impacting patients' quality of life. Although once viewed primarily as an immunoglobulin E-mediated condition, approximately 50% of patients with VKC do not exhibit allergic sensitization. It is now recognized that the immunopathology of VKC involves multiple inflammatory pathways that lead to the signs, symptoms, and conjunctival eosinophilic and fibroproliferative lesions that are a hallmark of the disease. We examine the evolution of our understanding of the immunopathology of VKC, the expanding VKC treatment armamentarium, the clinical implications of emerging treatment approaches, and future directions for VKC research and practice.
Topics: Child; Humans; Conjunctivitis, Allergic; Cyclosporine; Quality of Life; Conjunctiva; Ophthalmic Solutions
PubMed: 37890678
DOI: 10.1016/j.survophthal.2023.10.008 -
Sleep Medicine Apr 2024Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Pediatric obstructive sleep apnea (OSA) is a common disease that can have significant negative impacts on a child's health and development. A comprehensive evaluation of different pharmacologic interventions for the treatment of OSA in children is still lacking.
OBJECTIVE
This study aims to conduct a comprehensive systematic review and network meta-analysis of pharmacological interventions for the management of obstructive sleep apnea in pediatric population.
DATA SOURCES
PubMed, Web of Science, Embase, The Cochrane Library, and CNKI were searched from 1950 to November 2022 for pediatric OSA.
STUDY SELECTION
Multiple reviewers included Randomized controlled trials (RCTs) concerning drugs on OSA in children.
DATA EXTRACTION AND SYNTHESIS
Multiple observers followed the guidance of the PRISMA NMA statement for data extraction and evaluation. Bayesian network meta-analyses(fixed-effect model) were performed to compare the weighted mean difference (WMD), logarithmic odds ratios (log OR), and the surface under the cumulative ranking curves (SUCRA) of the included pharmacological interventions. Our protocol was registered in PROSPERO website (CRD42022377839).
MAIN OUTCOME(S) AND MEASURE(S)
The primary outcomes were improvements in the apnea/hypopnea index (AHI), while secondary outcomes included adverse events and the lowest arterial oxygen saturation (SaO2).
RESULTS
17 RCTs with a total of 1367 children with OSA aged 2-14 years that met the inclusion criteria were eventually included in our systematic review and network meta-analysis. Ten drugs were finally included in the study. The results revealed that Mometasone + Montelukast (WMD-4.74[95%CrIs -7.50 to -2.11], Budesonide (-3.45[-6.86 to -0.15], and Montelukast(-3.41[-5.45 to -1.39] exhibited significantly superior therapeutic effects compared to the placebo concerning apnea hypopnea index (AHI) value with 95%CrIs excluding no effect. Moreover, Mometasone + Montelukast achieved exceptionally high SUCRA values for both AHI (85.0 %) and SaO2 (91.0 %).
CONCLUSIONS AND RELEVANCE
The combination of mometasone furoate nasal spray and oral montelukast sodium exhibits the highest probability of being the most effective intervention. Further research is needed to investigate the long-term efficacy and safety profiles of these interventions in pediatric patients with OSA.
Topics: Child; Humans; Network Meta-Analysis; Acetates; Sleep Apnea, Obstructive; Mometasone Furoate; Cyclopropanes; Quinolines; Sulfides
PubMed: 38460418
DOI: 10.1016/j.sleep.2024.01.030 -
RSC Advances Nov 2023Supercritical carbon dioxide (SC-CO)-based approaches have become more popular in recent years as alternative methods for creating micro- or nanosized medicines....
Supercritical carbon dioxide (SC-CO)-based approaches have become more popular in recent years as alternative methods for creating micro- or nanosized medicines. Particularly, high drug solubility is required in those techniques using SC-CO as a solvent. During the most recent pandemic years, favipiravir and montelukast were two of the most often prescribed medications for the treatment of COVID-19. In this study, ethanol at 1 and 3 mol% was utilized as a cosolvent to increase the solubility of both medicines in SC-CO by a static approach using a range of temperatures (308 to 338 K) and pressure (12 to 30 MPa) values. The experimentally determined solubilities of favipiravir and montelukast in SC-CO + 3 mol% ethanol showed solubility values up to 33.3 and 24.5 times higher than that obtained for these drugs with only SC-CO. The highest values were achieved in the pressure of 12 MPa and temperature of 338 K. Last but not least, six density-based semi-empirical models with various adjustable parameters were used to perform the modeling of the solubility of favipiravir and montelukast.
PubMed: 38020033
DOI: 10.1039/d3ra05484e -
Current Hypertension Reviews 2024Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are...
BACKGROUND
Declined kidney function associated with hypertension is a danger for cognitive deficits, dementia, and brain injury. Cognitive decline and vascular dementia (VaD) are serious public health concerns, which highlights the urgent need for study on the risk factors for cognitive decline. Cysteinyl leukotriene (CysLT) receptors are concerned with regulating cognition, motivation, inflammatory processes, and neurogenesis.
OBJECTIVE
This research aims to examine the consequence of montelukast (specific CysLT antagonist) in renovascular hypertension 2-kidney-1-clip-2K1C model-triggered VaD in experimental animals.
METHODS
2K1C tactics were made to prompt renovascular hypertension in mature male rats. Morris water maze was employed to measure cognition. Mean arterial pressure (MAP), serum nitrite levels, aortic superoxide content, vascular endothelial activity, brain's oxidative stress (diminished glutathione, raised lipid peroxides), inflammatory markers (IL-10, IL-6, TNF-α), cholinergic activity (raised acetylcholinesterase), and cerebral injury (staining of 2, 3, 5- triphenylterazolium chloride) were also examined.
RESULTS
Montelukast in doses of 5.0 and 10.0 mg kg was used intraperitoneally as the treatment drug. Along with cognitive deficits, 2K1C-operated rats showed elevated MAP, endothelial dysfunction, brain oxidative stress, inflammation, and cerebral damage with diminished serum nitrite/nitrate. Montelukast therapy significantly and dose-dependently mitigated the 2K1Chypertension- provoked impaired behaviors, biochemistry, endothelial functions, and cerebral infarction.
CONCLUSION
The 2K1C tactic caused renovascular hypertension and associated VaD, which was mitigated via targeted regulation of CysLT receptors by montelukast administration. Therefore, montelukast may be taken into consideration for the evaluation of its complete potential in renovascular-hypertension-induced VaD.
Topics: Animals; Sulfides; Cyclopropanes; Acetates; Quinolines; Male; Dementia, Vascular; Leukotriene Antagonists; Oxidative Stress; Hypertension, Renovascular; Disease Models, Animal; Endothelium, Vascular; Receptors, Leukotriene; Inflammation Mediators; Cognition; Rats, Wistar; Brain; Rats; Maze Learning
PubMed: 38192137
DOI: 10.2174/0115734021276985231204092425 -
Brain Research Oct 2023Neuroinflammation plays an important role in brain injury and repair. Regulation of post-stroke inflammation may be a reasonable strategy to treat ischemic stroke. The...
BACKGROUND
Neuroinflammation plays an important role in brain injury and repair. Regulation of post-stroke inflammation may be a reasonable strategy to treat ischemic stroke. The present study demonstrates that montelukast sodium protected brain tissue by regulating the post-stroke inflammatory reaction.
METHODS
Adult male mice underwent distal occlusion of the middle cerebral artery (d-MCAO) surgery, followed by intraperitoneal injection of montelukast sodium or equivalent saline, from day 0-7 after the operation. On the 7th day, Rotarod and adhesive-removal test were performed. M AP2 staining, and Iba1, CD206, and CD16/32 co staining were performed. BV2 microglial cell lines were co-cultured with different concentrations of montelukast sodium with or without lipopolysaccharide (LPS). Real-time polymerase chain reaction (rt-PCR) and enzyme linked immunosorbent assay (ELISA) were used to detect the mRNA expression of M1 and M2 phenotypic microglia markers and the release of cytokines representing from different phenotypes of microglia cells.
RESULTS
Montelukast sodium prolonged the time that d-MCAO mice remained on the rotating bar, shortened the time to remove the sticker on the opposite claw, and reduced the infarct volume, promoting the transformation of microglial cells/macrophages around the infarct to the M2 phenotype. Montelukast sodium increased the mRNA expression of Arg-1, CD206, TGF-β, and IL-10 in BV2 microglial cell lines stimulated by LPS, while decreased the expression of iNOS, TNF-α, and CD16/32.
CONCLUSION
Montelukast sodium can protect against focal cerebral ischemic injury by regulating inflammatory reaction via promoting microglia polarization.
Topics: Mice; Male; Animals; Microglia; Lipopolysaccharides; Stroke; Brain Ischemia; Inflammation; Brain Injuries; Infarction; RNA, Messenger; Infarction, Middle Cerebral Artery
PubMed: 37499731
DOI: 10.1016/j.brainres.2023.148498 -
Annals of Allergy, Asthma & Immunology... Sep 2023The high prescription drug cost in the United States may negatively affect patient prognosis and treatment compliance.
BACKGROUND
The high prescription drug cost in the United States may negatively affect patient prognosis and treatment compliance.
OBJECTIVE
To fill the knowledge gap and inform clinicians regarding rhinology medications price changes by evaluating trends in price changes of highly used nasal sprays and allergy medications.
METHODS
The 2014-2020 Medicaid National Average Drug Acquisition Cost database was queried for drug pricing information for the following classes of medications: intranasal corticosteroids, oral antihistamines, antileukotrienes, intranasal antihistamines, and intranasal anticholinergics. Individual medications were identified by Food and Drug Administration-assigned National Drug Codes. Per unit, drug prices were analyzed for average annual prices, average annual percentage price changes, and inflation-adjusted annual and composite percentage price changes.
RESULTS
Beclometasone (Beconase AQ, 56.7%, QNASL, 77.5%), flunisolide (Nasalide, -14.6%), budesonide (Rhinocort Aqua, -1.2%), fluticasone (Flonase, -6.8%, Xhance, 11.7%), mometasone (Nasonex, 38.2%), ciclesonide (Omnaris, 73.8%), combination azelastine and fluticasone (Dymista, 27.3%), loratadine (Claritin, -20.5%), montelukast (Singulair, 14.5%), azelastine (Astepro, 21.9%), olopatadine (Patanase, 27.3%), and ipratropium bromide (Atrovent, 56.6%) had an overall change in inflation-adjusted per unit cost between 2014 and 2020 (% change). Of 14 drugs evaluated, 10 had an increase in inflation-adjusted prices, for an average increase of 42.06% ± 22.27%; 4 of 14 drugs had a decrease in inflation-adjusted prices, for an average decrease of 10.78% ± 7.36%.
CONCLUSION
The rising cost of highly used medications contributes to increased patient acquisition costs and may pose barriers of drug adherence to particularly vulnerable populations.
Topics: Humans; United States; Fluticasone; Administration, Intranasal; Mometasone Furoate; Adrenal Cortex Hormones; Histamine Antagonists; Loratadine; Beclomethasone
PubMed: 37098404
DOI: 10.1016/j.anai.2023.04.013 -
The Journal of Allergy and Clinical... Dec 2023Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events...
The Risk of Neuropsychiatric Adverse Events With Use of Leukotriene Receptor Antagonists in Patients With Asthma: Analysis of Korea's National Health Insurance Sharing Service Database.
BACKGROUND
Montelukast, a selective leukotriene receptor antagonist, is a commonly prescribed allergy medication but its potential association with neuropsychiatric adverse events is concerning.
OBJECTIVE
To analyze Korea's National Health Insurance System claims records to identify the risk of neuropsychiatric adverse events in patients with asthma treated with montelukast.
METHODS
This retrospective population-based study analyzed the National Health Insurance claims records of the entire Korean population between 2008 and 2015. We compared the risk of neuropsychiatric adverse events among patients with asthma using inhaled corticosteroids and/or long-acting β2-agonists with montelukast or pranlukast and those not using leukotriene receptor antagonists (control group).
RESULTS
There was no increased risk of the composite outcome of all measured neuropsychiatric adverse events in patients with asthma who were prescribed montelukast or pranlukast compared with those who were not. However, montelukast use was associated with an increased risk of hallucinations (inverse probability treatment weighting hazard ratio, 1.45; 95% CI, 1.07-1.96) and attention problems (inverse probability treatment weighting hazard ratio, 1.24; 95% CI, 1.01-1.52). Significant negative hazards for disorientation, anxiety, stress reactions, and somatic symptoms were observed in the montelukast group. When grouped by sex, the risk of hallucinations and attention problems was higher in men prescribed montelukast compared with the controls.
CONCLUSIONS
We did not observe an increase in all neuropsychiatric adverse events in the leukotriene receptor antagonist-treated group; however, an increased risk of hallucinations and attention problems was observed in those taking montelukast, regardless of the medication administration period.
Topics: Male; Humans; Leukotriene Antagonists; Retrospective Studies; Asthma; Quinolines; Acetates; National Health Programs; Hallucinations; Republic of Korea; Anti-Asthmatic Agents
PubMed: 37660732
DOI: 10.1016/j.jaip.2023.08.037