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Journal of Chromatographic Science Dec 2023Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for...
Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for simultaneous determination of montelukast sodium (MKT) and loratadine (LRT). The first method was based on chromatographic separation performed on precoated silica gel 60 GF254 plates with ethyl acetate-ethanol 9: 1 (v/v) as the mobile phase. The developed plates were scanned and quantified at 260 nm. The method gives linear correlation over concentration ranges of 0.3-3.6 μg/spot and 0.2-4.0 μg/spot for MKT and LRT, respectively. It was also successfully applied to analysis of both drugs in their pharmaceutical preparation and human plasma. The other methods are UV-spectrophotometric methods based on smart spectra manipulating to zero order spectrum of each drug. These methods are named response correlation (RC), a-centering and ratio derivative methods. RC and a-centering methods were dependent on the presence of an isosbestic point between the overlapped spectra of both drugs. While ratio derivative method based on manipulation of the ratio spectra of both drugs. The two drugs obey Beer-Lambert law over the concentration ranges of 3.0-30.0 μg/mL in the three spectrophotometric methods. Moreover, the greenness of the developed methods is assessed using suitable analytical Eco-Scale and Green Analytical Procedure Index.
Topics: Humans; Loratadine; Spectrophotometry; Quinolines; Densitometry
PubMed: 37032124
DOI: 10.1093/chromsci/bmad025 -
MedRxiv : the Preprint Server For... May 2024The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain.
IMPORTANCE
The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain.
OBJECTIVE
To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19.
DESIGN SETTING AND PARTICIPANTS
The ACTIV-6 platform randomized clinical trial aims to evaluate the effectiveness of repurposed medications in treating mild to moderate COVID-19. Between January 27, 2023, and June 23, 2023, 1250 participants ≥30 years of age with confirmed SARS-CoV-2 infection and ≥2 acute COVID-19 symptoms for ≤7 days, were included across 104 US sites to evaluate the use of montelukast.
INTERVENTIONS
Participants were randomized to receive montelukast 10 mg once daily or matched placebo for 14 days.
MAIN OUTCOMES AND MEASURES
The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID clinical progression scale; and difference in mean time unwell.
RESULTS
Among participants who were randomized and received study drug, the median age was 53 years (IQR 42-62), 60.2% were female, 64.6% identified as Hispanic/Latino, and 56.3% reported ≥2 doses of a SARS-CoV-2 vaccine. Among 628 participants who received montelukast and 622 who received placebo, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR] 1.02; 95% credible interval [CrI] 0.92-1.12; P(efficacy) = 0.63]). Unadjusted median time to sustained recovery was 10 days (95% confidence interval 10-11) in both groups. No deaths were reported and 2 hospitalizations were reported in each group; 36 participants reported healthcare utilization events (a priori defined as death, hospitalization, emergency department/urgent care visit); 18 in the montelukast group compared with 18 in the placebo group (HR 1.01; 95% CrI 0.45-1.84; P(efficacy)=0.48). Five participants experienced serious adverse events (3 with montelukast and 2 with placebo).
CONCLUSIONS AND RELEVANCE
Among outpatients with mild to moderate COVID-19, treatment with montelukast does not reduce duration of COVID-19 symptoms.
TRIAL REGISTRATION
ClinicalTrials.gov ( NCT04885530 ).
PubMed: 38798524
DOI: 10.1101/2024.05.16.24307115 -
Pharmaceutics Jul 2023Earlier studies with montelukast (M) and telmisartan (T) have revealed their potential antiviral properties against SARS-CoV-2 wild-type (WT) but have not assessed their...
Earlier studies with montelukast (M) and telmisartan (T) have revealed their potential antiviral properties against SARS-CoV-2 wild-type (WT) but have not assessed their efficacy against emerging Variants of Concern (VOCs) such as Omicron. Our research fills this gap by investigating these drugs' impact on VOCs, a topic that current scientific literature has largely overlooked. We employed computational methodologies, including molecular mechanics and machine learning tools, to identify drugs that could potentially disrupt the SARS-CoV-2 spike RBD-ACE2 protein interaction. This led to the identification of two FDA-approved small molecule drugs, M and T, conventionally used for treating asthma and hypertension, respectively. Our study presents an additional potential use for these drugs as antivirals. Our results show that both M and T can inhibit not only the WT SARS-CoV-2 but also, in the case of M, the Omicron variant, without reaching cytotoxic concentrations. This novel finding fills an existing gap in the literature and introduces the possibility of repurposing these drugs for SARS-CoV-2 VOCs, an essential step in responding to the evolving global pandemic.
PubMed: 37514075
DOI: 10.3390/pharmaceutics15071891 -
Naunyn-Schmiedeberg's Archives of... Feb 2024The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial... (Review)
Review
The microbiome is increasingly implicated in playing a role in physiology and pharmacology; in this review, we investigate the literature on the possibility of bacterial influence on the pharmacology of anti-asthmatic drugs, and the potential impact this has on asthmatic patients. Current knowledge in this area of research reveals an interaction between the gut and lung microbiome and the development of asthma. The influence of microbiome on the pharmacokinetics and pharmacodynamics of anti-asthmatic drugs is limited; however, understanding this interaction will assist in creating a more efficient treatment approach. This literature review highlighted that bioaccumulation and biotransformation in the presence of certain gut bacterial strains could affect drug metabolism in anti-asthmatic drugs. Furthermore, the bacterial richness in the lungs and the gut can influence drug efficacy and could also play a role in drug response. The implications of the above findings suggest that the microbiome is a contributing factor to an individuals' pharmacological response to anti-asthmatic drugs. Hence, future directions for research should follow investigating how these processes affect asthmatic patients and consider the role of the microbiome on drug efficacy and modify treatment guidelines accordingly.
Topics: Humans; Anti-Asthmatic Agents; Microbiota; Asthma; Lung; Bacteria
PubMed: 37650889
DOI: 10.1007/s00210-023-02681-5 -
Frontiers in Cellular and Infection... 2024Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is a prevalent condition that significantly impacts public health. Unfortunately, there are few effective treatment options available. Mendelian randomization (MR) has been utilized to repurpose existing drugs and identify new therapeutic targets. The objective of this study is to identify novel therapeutic targets for COPD.
METHODS
Cis-expression quantitative trait loci (cis-eQTL) were extracted for 4,317 identified druggable genes from genomics and proteomics data of whole blood (eQTLGen) and lung tissue (GTEx Consortium). Genome-wide association studies (GWAS) data for doctor-diagnosed COPD, spirometry-defined COPD (Forced Expiratory Volume in one second [FEV1]/Forced Vital Capacity [FVC] <0.7), and FEV1 were obtained from the cohort of FinnGen, UK Biobank and SpiroMeta consortium. We employed Summary-data-based Mendelian Randomization (SMR), HEIDI test, and colocalization analysis to assess the causal effects of druggable gene expression on COPD and lung function. The reliability of these druggable genes was confirmed by eQTL two-sample MR and protein quantitative trait loci (pQTL) SMR, respectively. The potential effects of druggable genes were assessed through the phenome-wide association study (PheWAS). Information on drug repurposing for COPD was collected from multiple databases.
RESULTS
A total of 31 potential druggable genes associated with doctor-diagnosed COPD, spirometry-defined COPD, and FEV1 were identified through SMR, HEIDI test, and colocalization analysis. Among them, 22 genes (e.g., MMP15, PSMA4, ERBB3, and LMCD1) were further confirmed by eQTL two-sample MR and protein SMR analyses. Gene-level PheWAS revealed that ERBB3 expression might reduce inflammation, while GP9 and MRC2 were associated with other traits. The drugs Montelukast (targeting the MMP15 gene) and MARIZOMIB (targeting the PSMA4 gene) may reduce the risk of spirometry-defined COPD. Additionally, an existing small molecule inhibitor of the APH1A gene has the potential to increase FEV.
CONCLUSIONS
Our findings identified 22 potential drug targets for COPD and lung function. Prioritizing clinical trials that target these identified druggable genes with existing drugs or novel medications will be beneficial for the development of COPD treatments.
Topics: Pulmonary Disease, Chronic Obstructive; Humans; Mendelian Randomization Analysis; Drug Repositioning; Quantitative Trait Loci; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38660492
DOI: 10.3389/fcimb.2024.1386506 -
Frontiers in Pharmacology 2023Loratadine and montelukast are clinical first-line drugs in the treatment of allergic rhinitis (AR). However, there is no clear evidence of the efficacy of loratadine...
Loratadine and montelukast are clinical first-line drugs in the treatment of allergic rhinitis (AR). However, there is no clear evidence of the efficacy of loratadine combined with montelukast in the treatment of AR. This study aimed to evaluate the efficacy and safety of the loratadine-montelukast combination on AR. In this meta-analysis, searches were conducted on PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure (CNKI). The search terms included loratadine, montelukast, allergic rhinitis, and clinical trials. Meta-analyses were conducted using Rev Man 5.3 and Stata 15 statistical software. A total of 23 studies with 4,902 participants were enrolled. For the primary outcome, pooled results showed that loratadine-montelukast can significantly reduce total nasal symptom scores (TNSS), when compared with loratadine (SMD, -1.00; 95% CI, -1.35 to -0.65, < 0.00001), montelukast (SMD, -0.46; 95% CI, -0.68 to -0.25, < 0.0001), or placebo (SMD, -0.93; 95% CI, -1.37 to -0.49, < 0.00001). For secondary outcomes, pooled results showed that compared with loratadine, loratadine-montelukast can significantly improve nasal congestion, nasal itching, nasal sneezing, nasal rhinorrhea, and rhinoconjunctivitis quality of life questionnaires (RQLQ). Compared with montelukast, loratadine-montelukast can significantly improve nasal itching, and nasal sneezing. Compared with placebo, loratadine-montelukast can significantly improve nasal congestion, and RQLQ. Loratadine-montelukast combination is superior to loratadine monotherapy, montelukast monotherapy, or placebo in improving AR symptoms. Therefore, loratadine-montelukast combination can be an option for patients with moderate-severe AR or poorly response to monotherapy. Systematic review registration number: clinicaltrials.gov, identifier CRD42023397519.
PubMed: 37915414
DOI: 10.3389/fphar.2023.1287320 -
Iranian Journal of Kidney Diseases Jul 2023Rhabdomyolysis is a clinical syndrome accompanied with biochemical changes that is diagnosed in some patients with acute chemical or drug poisoning. In this regard, the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Rhabdomyolysis is a clinical syndrome accompanied with biochemical changes that is diagnosed in some patients with acute chemical or drug poisoning. In this regard, the present study aimed to evaluate the effects of Montelukast in the treatment of intoxication-induced rhabdomyolysis.
METHODS
This single-blind randomized clinical trial study was conducted in Loghman Hakim Hospital from March 2021 to March 2022. The study participants were 60 individuals evenly distributed into experimental and control groups. The experimental group received Montelukast plus routine treatment and the control group Creatine phosphokinase (CPK), urea, creatinine, aspartate aminotransferase (AST) and alanine transaminase (ALT) levels were monitored daily in both groups for seven days. The variables of age, gender and history of diabetes mellitus and kidney diseases were recorded.
RESULTS
The mean age was 39.9 ± 16.87 and 38.2 ± 16.3 years in the control and intervention groups, respectively. Montelukast significantly (P < .05) reduced CPK levels on days five and seven, urea on days three, four, five and seven, and creatinine on days two to seven. The AST and ALT levels, unlike the control group which has a decreasing trend, increased first in the Montelukast group and then decreased on the sixth and seventh days.
CONCLUSION
The results showed that Montelukast effectively reduced CPK, urea and creatinine levels, as well as the recovery time in patients with poison-induced rhabdomyolysis. In other words, Montelukast is effective in the treatment of rhabdomyolysis. DOI: 10.52547/ijkd.7222.
Topics: Humans; Young Adult; Adult; Middle Aged; Creatinine; Single-Blind Method; Acetates; Cyclopropanes
PubMed: 37634246
DOI: No ID Found -
International Journal of Biological... 2024Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory...
Cysteinyl leukotriene receptor 1 (CYSLTR1) is observed to increase in psoriatic skin lesions. Montelukast, a CYSLTR1 antagonist, effectively treats inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, and atopic dermatitis. Thus, blocking CYSLTR1 may be a promising strategy for psoriasis immunotherapy. We prepared a montelukast sodium cream and solution and investigated their effects on psoriasis-like skin lesions induced by imiquimod (IMQ). After the treatment, serum, skin, and spleen samples were collected for evaluation. We treated human T helper (Th) 17 cells with montelukast to study its effect on Th17 differentiation and nuclear factor kappa-B (NF-κB) signaling. We also created a keratinocyte proliferation model induced by M5 cytokines and assessed the influence of montelukast on key psoriasis-related genes. We induced psoriasis in CYSLTR1 knockout (KO) mice using IMQ to explore the role of CYSLTR1 in psoriasis development. Montelukast sodium cream and solution effectively reduced the psoriasis area and severity index (PASI) and alleviated disease symptoms in IMQ-induced mice. Furthermore, reduced infiltration of inflammatory cells (Th1, Th17, and T follicular helper [Tfh] cells), decreased mRNA expression of cytokines in the skin (interleukin [IL]-17/F and IL-23), and lower serum concentrations of various cytokines (IL-2, IL-6, IL-13, and IL-17A/F) were observed. Montelukast cream and solution also decreased spleen size and the proportion of Th17 and Tfh cells, and significantly inhibited NF-κB signaling-related genes after application. Moreover, montelukast inhibited Th17 cell differentiation and suppressed NF-κB signaling . CYSLTR1 KO mice induced with IMQ showed improvement in PASI scores, serum IL-17A/F levels, and lower Th1 and Th17 cells in the spleen and skin compared to wild-type mice. Montelukast also suppressed the proliferation and inflammatory response of keratinocytes by regulating NF-κB signaling. Collectively, our results strongly indicate that inhibition of CYSLTR1 signaling to target the Th17 response holds significant promise as a therapeutic approach to manage psoriasis.
Topics: Humans; Animals; Mice; NF-kappa B; Interleukin-17; Th17 Cells; Psoriasis; Cell Differentiation; Cytokines; Acetates; Cyclopropanes; Quinolines; Sulfides
PubMed: 38617532
DOI: 10.7150/ijbs.92514 -
Clinical Otolaryngology : Official... Jul 2024Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Leukotrienes play a significant role in the pathogenesis of adenoid hypertrophy (A.H.). Therefore, we aimed to analyse the role of montelukast, a leukotriene receptor antagonist, alone or in combination with mometasone, a potent local intranasal steroid, for the treatment of A.H.
METHODS
Participants were children with A.H. were treated with montelukast alone or montelukast and mometasone furoate. The main outcome measures were effect of montelukast on clinical symptoms of A.H. A literature review was conducted using online search engines, Cochrane Library, PubMed, Web of Science and Scopus, for randomized clinical trials assessing children with A.H. treated with montelukast alone or montelukast and mometasone furoate. Seven randomized clinical trials (RCTs) were included with 742 children.
RESULTS
Our study reveals that montelukast alone or in combination with intranasal mometasone furoate significantly improves clinical symptoms of adenoid hypertrophy such as snoring, sleeping disturbance, mouth breathing and A/N ratio. Montelukast was superior to placebo in decreasing snoring (SMD = -1.00, 95% CI [-1.52, -0.49]), sleep discomfort (SMD = -1.26, 95% CI [-1.60, -0.93]), A/N ratio (MD = -0.11, 95% CI [-0.14, -0.09]) and mouth breathing (SMD = -1.36, 95% CI [-1.70, -1.02]). No difference was detected between montelukast and mometasone versus mometasone alone in snoring (SMD = -0.21, 95%CI [-0.69, 0.27]); however, the combination group was superior to the mometasone alone in mouth breathing (SMD = -0.46, 95% CI [-0.73, -0.19]).
CONCLUSIONS
The limitation of studies included a small sample size, with an overall low to medium quality. Thus, further larger, higher-quality RCTs are recommended to provide more substantial evidence.
Topics: Humans; Adenoids; Cyclopropanes; Quinolines; Acetates; Sulfides; Hypertrophy; Child; Mometasone Furoate; Leukotriene Antagonists; Administration, Intranasal; Drug Therapy, Combination; Treatment Outcome
PubMed: 38700144
DOI: 10.1111/coa.14169 -
Clinical Rheumatology Jun 2024The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is... (Review)
Review
The association between the use of certain medications (including sulfonamides, hydralazine, and procainamide) and the occurrence of drug-induced lupus or hepatitis is well established. More recently, cases of immune-related adverse events ranging from inflammatory polyarthritis to necrotizing myositis in patients taking checkpoint inhibitors have been reported. However, data linking drugs to systemic vasculitis are scarce and at times debatable. Propylthiouracil, hydralazine, and minocycline have been associated with rare cases of ANCA-associated syndromes, including life-threatening pulmonary-renal syndromes and systemic polyarteritis nodosa-like diseases. Eosinophilic granulomatosis with polyangiitis (EGPA) has been reported in patients taking leukotriene inhibitors. Since the link between the use of leukotriene inhibitors and occurrence of EGPA remains highly controversial, we performed a literature review for cases of EGPA in patients taking montelukast without prior history of oral corticosteroid use. We found 24 cases, along with our own two cases described, making 26 cases in total. The mean age was 43 and a majority (18/26) were female. In majority of cases EGPA-like disease never relapsed after they were taken off leukotriene inhibitors suggesting a clear causal relationship between the use of these drugs and occurrence of eosinophil-rich systemic EGPA.
Topics: Humans; Sulfides; Quinolines; Cyclopropanes; Acetates; Leukotriene Antagonists; Female; Churg-Strauss Syndrome; Male; Granulomatosis with Polyangiitis; Middle Aged; Adult
PubMed: 38720163
DOI: 10.1007/s10067-024-07000-8