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The Journal of Pediatric Pharmacology... 2024
PubMed: 38332955
DOI: 10.5863/1551-6776-29.1.90 -
PLoS Neglected Tropical Diseases Feb 2024Montelukast has shown potential as a candidate treatment for dengue. This study aimed to evaluate the efficacy and safety of montelukast in preventing dengue with... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Montelukast has shown potential as a candidate treatment for dengue. This study aimed to evaluate the efficacy and safety of montelukast in preventing dengue with warning signs.
METHODS
This multicenter, randomized, double-blind, placebo-controlled trial enrolled adult participants with NS1 antigenemia in Thailand. The participants were randomly assigned to receive either oral montelukast (10 mg) or a placebo for 10 days or until all symptoms resolved.
RESULTS
Between January 2021 and June 2023, 358 participants were enrolled and randomly assigned (1:1) to receive either montelukast or placebo. The incidence rate of warning signs in the montelukast group and the placebo group were 9.5% and 7.8% per day, respectively. There was no difference between the two groups (HR 1.36; 95%CI 0.94-1.96, P = 0.105). No statistically significant differences were observed in the incidence rate of severe dengue, hemoconcentration, thrombocytopenia, admission, or recovery from dengue. Neither dengue shock, nor mortality occurred. The montelukast group exhibited a decreased incidence rate of transaminase elevations (0.7% vs 1.4% per day, HR: 0.48, 95%CI 0.25-0.90, P = 0.023).
CONCLUSION
Oral montelukast does not reduce the incidence of warning signs among patients with dengue. Nevertheless, the observed decrease in transaminase elevations warrants further investigation to evaluate the potential effect of montelukast.
CLINICAL TRIALS REGISTRATION
Clinicaltrials.gov, NCT04673422, registered on 9 December 2020.
Topics: Adult; Humans; Treatment Outcome; Acetates; Double-Blind Method; Severe Dengue; Transaminases; Cyclopropanes; Quinolines; Sulfides
PubMed: 38306389
DOI: 10.1371/journal.pntd.0011927 -
Journal of Orthopaedic Translation Jan 2024Arthrofibrosis (AF) is a fibrotic joint disease resulting from excessive collagen production and fibrous scar formation after total knee arthroplasty (TKA). This...
BACKGROUND
Arthrofibrosis (AF) is a fibrotic joint disease resulting from excessive collagen production and fibrous scar formation after total knee arthroplasty (TKA). This devastating complication may cause consistent pain and dramatically reduction of functionality. Unfortunately, the conservative treatments to prevent the AF in the early stage are largely unknown due to the lack of specific biomarkers and reliable therapeutic targets.
METHODS
In this study, we extracted1782 fibrosis related genes (FRGs) from 373,461published literature based on the large natural language processing models (ChatGPT) and intersected with the 2750 differential expressed genes (DEGs) from mRNA microarray (GSE135854). A total of 311 potential AF biomarker genes (PABGs) were obtained and functional analysis were performed including gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Subsequently, we accomplished validation in AF animal models with immobilization of the unilateral knee joints of 16 rabbits for 1-week, 2-weeks, 3-weeks and 4-weeks. Finally, we tested the biomarkers in a retrospective cohort enrolled 35 AF patients and 35 control group patients.
RESULTS
We identified G-protein-coupled receptor 17 (GPR17) as a reliable therapeutic biomarker for AF diagnosis with higher AUC (0.819) in the ROC curve. A total of 21 potential drugs targeted to GPR17 were screened. Among them, pranlukast and montelukast have achieved therapeutic effect in animal models. In addition, we established an online AF database for data integration (https://chenxi2023.shinyapps.io/afdbv1).
CONCLUSIONS
These results unveiling therapeutic biomarkers for AF diagnosis, and provide potential drugs for clinical treatment.
THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE
Our study demonstrated that GPR17 holds significant promise as a potential biomarker and therapeutic target for arthrofibrosis. Moreover, pranlukast and montelukast targeted to GPR17 that could be instrumental in the treatment of AF.
PubMed: 38304615
DOI: 10.1016/j.jot.2023.11.002 -
AACE Clinical Case Reports 2024Patients with systemic mastocytosis are at high risk of developing osteoporosis and fractures. Herein, we report a case of hip fragility fracture in a patient with...
BACKGROUND/OBJECTIVE
Patients with systemic mastocytosis are at high risk of developing osteoporosis and fractures. Herein, we report a case of hip fragility fracture in a patient with indolent systemic mastocytosis and normal bone density.
CASE REPORT
A 48-year-old man experienced a left femoral neck fracture after a fall. After a dose of oxycodone/hydromorphone postoperatively, he developed an anaphylactic reaction. Previously, he experienced a few other episodes of flushing, dizziness, and syncope precipitated by stress and alcohol. His examination was notable for pink and brown macules on his chest, back, arms, and legs. His laboratory test revealed a markedly elevated tryptase level of 171 ng/mL (<11 ng/mL). Treatment including cetirizine, montelukast, and ranitidine controlled his symptoms. His bone density test result was normal. Ten months after hip surgery, his c-terminal telopeptide of collagen type 1 and bone-specific alkaline phosphatase levels significantly increased. The bone scan demonstrated diffusely increased radiotracer uptake throughout the osseous structures. Given high bone turnover and the prior hip fracture, he received zoledronic acid yearly for 3 years, and no further fractures have occurred.
DISCUSSION
The case is unusual as the fracture occurred despite normal bone density and significant osteosclerosis, which was previously considered protective against fractures. Additionally, rather than the spine, the fracture occurred in the hip, which is an uncommon site for mastocytosis-induced fractures.
CONCLUSION
Mastocytosis is a rare cause of osteoporosis, and it is important to keep this condition in the differential diagnosis of osteoporosis, particularly when the fracture presentation is atypical.
PubMed: 38303771
DOI: 10.1016/j.aace.2023.10.003 -
Heliyon Jan 2024Montelukast, an approved leukotriene receptor 1 (Cys-LT 1) antagonist with anti-inflammatory properties is used for the treatment of asthma and allergic rhinitis. In the...
Anti-enzymatic and DNA docking studies of montelukast: A multifaceted molecular scaffold with investigations, molecular expression analysis and molecular dynamics simulations.
Montelukast, an approved leukotriene receptor 1 (Cys-LT 1) antagonist with anti-inflammatory properties is used for the treatment of asthma and allergic rhinitis. In the present studies, montelukast was subjected to inhibitory assays followed by kinetic and investigations. Montelukast demonstrated inhibitory activity against yeast α-glucosidase (IC 44.31 ± 1.21 μM), jack bean urease (JB urease, IC 8.72 ± 0.23 μM), human placental alkaline phosphatase (hPAP, IC 17.53 ± 0.19 μM), bovine intestinal alkaline phosphatase (bIAP, IC 15.18 ± 0.23 μM) and soybean 15-lipoxygenase (15-LOX, IC 2.41 ± 0.13 μM). Kinetic studies against α-glucosidase and urease enzymes revealed its competitive mode of inhibition. Molecular expression analysis of montelukast in breast cancer cell line MCF-7 down-regulated AP by a factor of 0.27 (5 μM) compared with the 0.26 value for standard inhibitor levamisole (10 μM). Molecular docking estimated a binding affinity ranging -8.82 to -15.65 kcal/mol for the enzymes. Docking against the DNA dodecamer (ID: 1BNA) observed -9.13 kcal/mol via minor groove binding. MD simulations suggested stable binding between montelukast and the target proteins predicting strong inhibitory potential of the ligand. Montelukast features a chloroquinoline, phenyl ring, a cyclopropane group, a carboxylic group and a sulfur atom all of which collectively enhance its inhibitory potential against the said enzymes. These and computational investigations demonstrate that it is possible and suggested that the interactions of montelukast with more than one targets presented herein may be linked with the side effects presented by this drug and necessitate additional work. The results altogether suggest montelukast as an important structural scaffold possessing multitargeted features and warrant further investigations in repurposing beyond its traditional pharmacological use.
PubMed: 38298631
DOI: 10.1016/j.heliyon.2024.e24470 -
BMC Chemistry Jan 2024In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current...
In the last few decades, green analytical chemistry (GAC) has become a smart magical solution for the qualification and quantification of many drugs. In the current study, a direct, sensitive, and green RP-HPLC method was used to separate three anti-histaminic combinations rupatadine/montelukast, desloratadine/montelukast, fexofenadine/montelukast, and finally a mixture of rupatadine and its metabolite; desloratadine in less than 20 min. The developed method was optimized by a 2 full factorial design to improve the chromatographic responses. The proposed method was used to analyze these antihistaminic combinations at different pharmaceutical ratios. The linearity range is from 1 to 10 µg/mL for rupatadine, desloratadine, and montelukast, while for fexofenadine from 1 to 24 µg/mL drugs. The proposed method is useful in common quality control analysis of the investigated quaternary combinations because of its non-toxic and eco-friendly effects on the environment and human beings. The proposed procedure was thoroughly validated in accordance with ICH guidelines and was revealed to be accurate, reproducible, and selective. The developed methods were compared with a reported reference comparison method, where no significant difference was observed.
PubMed: 38291482
DOI: 10.1186/s13065-024-01117-2 -
BMC Chemistry Jan 2024For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous...
For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous fluorescence, the current work developed a green, highly accurate, sensitive, and selective spectroscopic approach for estimating Montelukast sodium and Bilastine in pharmaceutical dosage form without previous separation. The selected technique focuses on measuring the synchronized fluorescence of the studied medications at a fixed wavelength range (Δλ) = 110 nm, and using the amplitude of the first derivative's peak at 381 and 324 nm, for quantitative estimation of Montelukast sodium and Bilastine, respectively. The impacts of different factors on the referred drugs' synchronized fluorescence intensity were investigated and adjusted. The calibration plots for were found to be linear over concentration ranges of 50-2000 ng mL for Montelukast sodium and 50-1000 ng mL for Bilastine. Montelukast sodium and Bilastine have LODs of 16.5 and 10.9 ng mL, respectively. In addition, LOQs were: 49.9 and 33.0 ng mL, for both drugs, respectively. The developed method was successfully employed to quantify the two drugs in synthetic tablets mixture and in laboratory prepared mixtures containing varied Montelukast and Bilastine ratios. To compare the results with the published analytical approach, a variance ratio F-test and a student t-test were used, which revealed no significant differences.
PubMed: 38268023
DOI: 10.1186/s13065-024-01116-3 -
Pharmaceuticals (Basel, Switzerland) Jan 2024Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a...
Montelukast (MTK), a potent antagonist of cysteinyl leukotriene receptor 1, has shown therapeutic promise for the treatment of neuropsychiatric disorders. Delirium, a common complication in critically ill patients, lacks effective treatment. This study aims to explore the impact of pre-intensive care unit (ICU) MTK use on in-hospital delirium incidence and, subsequent, prognosis in critically ill patients. A retrospective cohort study (n = 6344) was conducted using the MIMIC-IV database. After propensity score matching, logistic/Cox regression, E-value sensitivity analysis, and causal mediation analysis were performed to assess associations between pre-ICU MTK exposure and delirium and prognosis in critically ill patients. Pre-ICU MTK use was significantly associated with reduced in-hospital delirium (OR: 0.705; 95% CI 0.497-0.999; = 0.049) and 90-day mortality (OR: 0.554; 95% CI 0.366-0.840; = 0.005). The association was more significant in patients without myocardial infarction (OR: 0.856; 95% CI 0.383-0.896; = 0.014) and could be increased by extending the duration of use. Causal mediation analysis showed that the reduction in delirium partially mediated the association between MTK and 90-day mortality (ACME: -0.053; 95% CI -0.0142 to 0.0002; = 0.020). In critically ill patients, MTK has shown promising therapeutic benefits by reducing the incidence of delirium and 90-day mortality. This study highlights the potential of MTK, beyond its traditional use in respiratory disease, and may contribute to the development of novel therapeutic strategies for delirium.
PubMed: 38256958
DOI: 10.3390/ph17010125 -
American Journal of Translational... 2023This study was designed to determine the effects of montelukast sodium combined with budesonide on pulmonary function, serum immunoglobulin (Ig)E levels, and eosinophil...
OBJECTIVE
This study was designed to determine the effects of montelukast sodium combined with budesonide on pulmonary function, serum immunoglobulin (Ig)E levels, and eosinophil (EOS) percentage in children comorbid with allergic rhinitis (AR) and asthma.
METHODS
The medical records of 114 children comorbid with AR and asthma treated in the Guizhou Provincial People's Hospital from February 2020 to September 2022 were collected and analyzed retrospectively. Among them, 54 children treated with budesonide were assigned to a control group, and the remaining 60 children treated with montelukast sodium combined with budesonide were assigned to an observation group. The efficacy was compared between the two groups. Additionally, the changes in pulmonary function, serum IgE levels, and EOS percentage were compared between the two groups before and after treatment (one month). The adverse reactions during the treatment and the recurrence of AR within 3 months were recorded. Logistics regression was conducted to analyze the risk factors affecting the efficacy in children.
RESULTS
The observation group showed a significantly higher overall response rate than the control group (P<0.05). After treatment, the observation group showed significantly higher levels of forced expiratory volume in 1 second (FEV1)%, FEV1/forced vital capacity (FVC), and peak expiratory flow (PEF) than the control group (P<0.05), and significantly lower IgE levels and EOS percentage than the control group (P<0.05). No significant difference was found between the two groups in terms of the total incidence of adverse reactions (P>0.05). According to the follow-up results of prognosis, the observation group presented a greatly lower recurrence rate of AR within 3 months than the control group (P<0.05). Multivariate logistics regression analysis showed that therapeutic regimen, IgE, and EOS were independent risk factors affecting the efficacy in the patients (P<0.05).
CONCLUSION
Montelukast sodium combined with budesonide can substantially improve the pulmonary function in children with comorbid AR and asthma, alleviate their symptoms of asthma and rhinitis, and lower the IgE level and EOS percentage. In addition, therapeutic regimen, IgE and EOS are independent risk factors affecting the efficacy in patients.
PubMed: 38186993
DOI: No ID Found