Montelukast Research Articles

A rat model of adenoid hypertrophy constructed by using ovalbumin and lipopolysaccharides to induce allergy, chronic inflammation, and chronic intermittent hypoxia.

Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH. An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-β were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated. Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-β levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement. The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.

The contribution of the WNT pathway to the therapeutic effects of montelukast in experimental murine airway inflammation induced by ovalbumin and lipopolysaccharide.

The wingless/integrase-1 (WNT) pathway involved in the pathogenesis of inflammatory airway diseases has recently generated considerable research interest. Montelukast, a leukotriene receptor antagonist, provides therapeutic benefits in allergic asthma involving eosinophils. We aimed to investigate the role of the WNT pathway in the therapeutic actions of montelukast (MT) in a mixed type of allergic-acute airway inflammation model induced by ovalbumin (OVA) and lipopolysaccharide (LPS) in mice. Female mice were sensitized with intraperitoneal OVA-Al(OH)3 administration in the initiation phase and intranasal OVA followed by LPS administration in the challenge phase. The mice were divided into eight groups: control, asthmatic, and control/asthmatic treated with XAV939 (inhibitor of the canonical WNT pathway), LGK-974 (inhibitor of the secretion of WNT ligands), or MT at different doses. The inhibition of the WNT pathway prevented tracheal 5-HT and bradykinin hyperreactivity, while only the inhibition of the canonical WNT pathway partially reduced 5-HT and bradykinin contractions compared to the inflammation group. Therefore, MT treatment hindered 5-HT and bradykinin hyperreactivity associated with airway inflammation. Furthermore, MT prevented the increases in the phosphorylated GSK-3β and WNT5A levels, which had been induced by airway inflammation, in a dose-dependent manner. Conversely, the MT application caused a further increase in the fibronectin levels, while there was no significant alteration in the phosphorylation of the Smad-2 levels in the isolated lungs of the mice. The MT treatment reversed the increase in the mRNA expression levels of interleukin-17A. An increase in eosinophil and neutrophil counts was observed in bronchoalveolar lavage fluid samples obtained from the mice in the inflammation group, which was hampered by the MT treatment. The inhibition of the WNT pathway did not alter inflammatory cytokine expression or cell infiltration. The WNT pathway mediated the therapeutic effects of MT due to the inhibition of GSK-3β phosphorylation as well as the reduction of WNT5A levels in a murine airway inflammation model.

Formulation Development and Evaluation of Montelukast Sodium Paper Tablets for Enhanced Drug Release

In this study, the technique of paper-based tablets was evaluated for solubility enhancement of montelukast sodium (MS), an anti-asthmatic, Biopharmaceutical Classification System (BCS) class II medication. Initially, the potential for compressing regular paper into tablets was rigorously examined. Results demonstrated that paper may be utilised to make tablets, regardless of type of the paper utilized. The medicinal quality was satisfactory; and entire tablets of the batch met the Indian Pharmacopeia’s criteria. Compressing drug-loaded paper resulted in the formation of drug-loaded tablets. The MS loaded tablets prepared using kitchen roll paper delivered the best results. The tablet was disintegrated in 27 seconds, and drug release of MS was enhanced by 1.88 folds. The tablets were sufficiently hard, and they did not get broken during friability studies. Also, the tablets passed the other evaluation parameters. These paper tablets were also stable under accelerated storage conditions.

Clinical efficacy of montelukast sodium combination therapy for cough variant asthma in children: A meta-analysis.

This meta-analysis aims to assess the clinical effectiveness of combination therapy with montelukast sodium for the treatment of cough variant asthma (CVA) in children, intending to provide clinical evidence and data to guide the selection of clinical therapy. A literature review was conducted using numerous databases, including China National Knowledge Infrastructure (CNKI), Wanfang database, Embase, PubMed, and Web of Science, from inception to December 2023. Trials meeting the criteria for the combined treatment of montelukast sodium for CVA in children were included. Stata 16.0 software was utilized for meta-analysis. The combined treatment group received montelukast sodium in addition to the control group, while the control group received budesonide, fluticasone propionate, salmeterol-fluticasone, or ketotifen alone. This investigation included 18 papers. All subjects were from the Chinese population. Compared to the control group, the combined treatment group demonstrated a higher effective rate (relative ratio [RR] = 1.23, 95% confidence interval [CI]: 1.18-1.29, p < .001), but no difference in the incidence of adverse reactions (RR = 0.65, 95%CI: 0.42-1.02, p = .060) after treatment. Moreover, the peak expiratory flow (PEF) (SMD = 1.69, 95%CI: 1.09-2.30, p < .001), forced vital capacity (FVC) (SMD = 1.67, 95%CI: 0.94-2.39, p < .001), forced expiratory volume in 1 s (FEV1) (SMD = 1.74, 95%CI: 1.09-2.40, p < .001), and FEV1/FVC (SMD = 1.84, 95%CI: 0.41-3.28, p = .012) were significantly higher in the combined treatment group than in the control group after treatment. Compared with the control group, the levels of tumor necrosis factor-α (SMD = -2.38, 95%CI: -3.22to -1.55, p < .001), IL-4 (SMD = -2.65, 95%CI: -3.26 to-2.04, p < .001), and IgE (SMD = -2.98, 95%CI: -3.24 to -2.72, p < .001) were significantly lower in the combined treatment group after treatment. The combined use of montelukast sodium in the treatment of pediatric CVA in China is associated with a significant clinical effect, making it a reasonable therapeutic approach.

Four chemometric models enhanced by Latin hypercube sampling design for quantification of anti-COVID drugs: sustainability profiling through multiple greenness, carbon footprint, blueness, and whiteness metrics

Montelukast sodium (MLK) and Levocetirizine dihydrochloride (LCZ) are widely prescribed medications with promising therapeutic potential against COVID-19. However, existing analytical methods for their quantification are unsustainable, relying on toxic solvents and expensive instrumentation. Herein, we pioneer a green, cost-effective chemometrics approach for MLK and LCZ analysis using UV spectroscopy and intelligent multivariate calibration. Following a multilevel multifactor experimental design, UV spectral data was acquired for 25 synthetic mixtures and modeled via classical least squares (CLS), principal component regression (PCR), partial least squares (PLS), and genetic algorithm-PLS (GA-PLS) techniques. Latin hypercube sampling (LHS) strategically constructed an optimal validation set of 13 mixtures for unbiased predictive performance assessment. Following optimization of the models regarding latent variables (LVs) and wavelength region, the optimum root mean square error of cross-validation (RMSECV) was attained at 2 LVs for the 210–400 nm spectral range (191 data points). The GA-PLS model demonstrated superb accuracy, with recovery percentages (R%) from 98 to 102% for both analytes, and root mean square error of calibration (RMSEC) and prediction (RMSEP) of (0.0943, 0.1872) and (0.1926, 0.1779) for MLK and LCZ, respectively, as well bias-corrected mean square error of prediction (BCMSEP) of -0.0029 and 0.0176, relative root mean square error of prediction (RRMSEP) reaching 0.7516 and 0.6585, and limits of detection (LOD) reaching 0.0813 and 0.2273 for MLK and LCZ respectively. Practical pharmaceutical sample analysis was successfully confirmed via standard additions. We further conducted pioneering multidimensional sustainability evaluations using state-of-the-art greenness, blueness, and whiteness tools. The method demonstrated favorable environmental metrics across all assessment tools. The obtained Green National Environmental Method Index (NEMI), and Complementary Green Analytical Procedure Index (ComplexGAPI) quadrants affirmed green analytical principles. Additionally, the method had a high Analytical Greenness Metric (AGREE) score (0.90) and a low carbon footprint (0.021), indicating environmental friendliness. We also applied blueness and whiteness assessments using the high Blue Applicability Grade Index (BAGI) and Red–Green–Blue 12 (RGB 12) algorithms. The high BAGI (90) and RGB 12 (90.8) scores confirmed the method's strong applicability, cost-effectiveness, and sustainability. This work puts forward an optimal, economically viable green chemistry paradigm for pharmaceutical quality control aligned with sustainable development goals.

NOVEL UV SPECTROPHOTOMETRIC METHOD FOR SIMULTANEOUS ESTIMATION OF MONTELUKAST SODIUM AND OLOPATADINE HYDROCHLORIDE USING ABSORBANCE CORRECTION PRINCIPLE

A simple, accurate and economical UV spectroscopic method has been developed for the simultaneous estimation of olopatadine hydrochloride and montelukast sodium. The developed method is based on the determination of the two drugs using UV absorbance correction principle. The wavelengths chosen for analysis were 352 nm for montelukast sodium (as absorbance due to the other drug was nil at this wavelength) and 298.5 nm for olopatadine hydrochloride (corrected for absorbance due to montelukast sodium) with water as diluent. The Beer-Lambert’s range for the two drugs was found to be 2-100 μg mL-1 at 298.5 nm and 2-70 μg mL-1 at 352 nm for montelukast sodium with r2 of ≥ 0.990. The developed method was validated as per ICH guidelines and the percentage assay results were within acceptable limits. The developed method can thus be successfully used for the regular analysis of olopatadine hydrochloride and montelukast sodium in bulk and in combination.

Effect and mechanism of Maxing Shigan Decoction on reducing inflammatory response in rats with cough variant asthma via TLR4/MyD88/NF-κB and p38 MAPK signaling pathways

This study aims to investigate the effect and mechanism of Maxingshigan Decoction on inflammation in the rat model of cough variant asthma(CVA). The SPF-grade SD rats of 6-8 weeks were randomized into normal, model, Montelukast sodium, and low-, medium-, and high-dose Maxing Shigan Decoction groups, with 8 rats in each group. The CVA rat model was induced by ovalbumin(OVA) and aluminum hydroxide sensitization and ovalbumin stimulation. The normal group and model group were administrated with equal volume of normal saline by gavage, and other groups with corresponding drugs by gavage. After the experiment, the number of white blood cells in blood and the levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α) in the serum were measured. The lung tissue was stained with hematoxylin-eosin(HE). Western blot was employed to determine the protein levels of nuclear factor-κB(NF-κB), Toll-like receptor 4(TLR4), myeloid differentiation protein(MyD88), and mitogen-activated protein kinase(MAPK) in the lung tissue. Real-time PCR was carried out to measure the mRNA levels of TLR4 and MyD88 in the lung tissue. Compared with the normal group, the model group showed increased white blood cells, elevated IL-6 and TNF-α levels(P&lt;0.01), lowered IL-10 level(P&lt;0.01), up-regulated protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK(P&lt;0.01) and mRNA levels of TLR4 and MyD88(P&lt;0.01) in the lung tissue. HE staining showed obvious infiltration of inflammatory cells around the airway and cell disarrangement in the model group. Compared with the model group, Montelukast sodium and high-dose Maxing Shigan Decoction reduced the white blood cells, lowered the IL-6 and TNF-α levels(P&lt;0.01), and elevated the IL-10 level(P&lt;0.01). Moreover, they down-regulated the protein levels of TLR4, MyD88, p-p65/NF-κB p65, p-p38 MAPK/p38 MAPK in the lung tissue(P&lt;0.01) and the mRNA levels of TLR4 and MyD88 in the lung tissue(P&lt;0.01). HE staining showed that Montelukast sodium and high-dose Maxing Shigan Decoction reduced inflammatory cell infiltration and cell disarrangement. The number of white blood cells, the levels of IL-10 and TNF-α in the serum, the protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK, and the mRNA levels of TLR4 and MyD88 in the lung tissue showed no significant differences between the Montelukast sodium group and high-dose Maxing Shigan Decoction group. Maxing Shigan Decoction can inhibit airway inflammation in CVA rats by inhibiting the activation of TLR4/MyD88/NF-κB and p38 MAPK signaling pathways.

Development of a green synchronous spectrofluorimetric technique for simultaneous determination of Montelukast sodium and Bilastine in pharmaceutical formulations

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−1 for Montelukast sodium and 50–1000 ng mL−1 for Bilastine. Montelukast sodium and Bilastine have LODs of 16.5 and 10.9 ng mL−1, respectively. In addition, LOQs were: 49.9 and 33.0 ng mL−1, 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.

Promising Effects of Montelukast for Critically Ill Asthma Patients via a Reduction in Delirium.

Background: 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. Methods: 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. Results: Pre-ICU MTK use was significantly associated with reduced in-hospital delirium (OR: 0.705; 95% CI 0.497-0.999; p = 0.049) and 90-day mortality (OR: 0.554; 95% CI 0.366-0.840; p = 0.005). The association was more significant in patients without myocardial infarction (OR: 0.856; 95% CI 0.383-0.896; p = 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; p = 0.020). Conclusions: 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.

CYSLTR1 antagonist inhibits Th17 cell differentiation by regulating the NF-κB signaling for the treatment of psoriasis.

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 in vitro 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 in vitro. 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.

Effect of Montelukast Sodium in Conjunction with Mometasone Furoate Aqueous Nasal Spray in Treating Allergic Rhinitis

Effect of Montelukast Sodium in Conjunction with Mometasone Furoate Aqueous Nasal Spray in Treating Allergic Rhinitis

Montelukast Sodium to Prevent and Treat Bronchopulmonary Dysplasia in Very Preterm Infants: A Quasi-Randomized Controlled Trial.

Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in preterm infants and lacks effective methods for prevention and treatment. The aim of this study is to explore the efficacy and safety of montelukast in preventing or treating BPD in preterm infants. The preterm infants with BPD risk factors were divided randomly into a montelukast group and a control group. In the montelukast group, preterm infants were given 1 mg/kg of montelukast sodium daily. There was no placebo in the control group. There was no significant difference in the incidence of moderate or severe BPD between the two groups (31.8% vs. 35%). The duration of respiratory support in the montelukast group was shorter than that in the control group (36.4 ± 12.8 d vs. 43.1 ± 15.9 d, p = 0.037). The pulmonary severity score (PSS) at 21 days of life in the montelukast group was significantly lower than that in the control group (0.56 ± 0.13 vs. 0.62 ± 0.14, p = 0.048). There were no significant differences in the duration of mechanical ventilation, length of stay, hospitalization expenses, or incidence of adverse events. Although montelukast cannot alleviate the severity of BPD, it may shorten the duration of respiratory support and decrease the PSS in very preterm infants. There were no significant adverse drug events associated with montelukast treatment.

Eco‐friendly synchronous fluorescence spectrofluorimetric method for simultaneous determination of montelukast sodium and fexofenadine hydrochloride in their antiallergic rhinitis fixed‐dose combination tablets

AbstractAn innovative, simple, accurate, sensitive, and eco‐friendly synchronous fluorescence spectrofluorimetric method has been developed for the simultaneous analysis of montelukast sodium (MON) and fexofenadine hydrochloride (FEX). The method relies on measuring the relative synchronous fluorescence intensity of both drugs using Δλ of 60 nm in methanol at 405 nm for MON and 288 nm for FEX. The experimental parameters influencing the developed method were investigated and optimized. The method was linear over the ranges 0.1–2.0 and 2.0–20.0 μg/ml for MON and FEX, respectively. The limits of detection were 0.018 and 0.441 μg/ml, and the limits of quantitation were 0.055 and 1.336 μg/ml for MON and FEX, respectively. The developed method was applied successfully for the determination of the two drugs in their newly released fixed‐dose combination prescribed for the treatment of allergic rhinitis. The mean per cent recoveries were found to be 100.680 ± 0.890 and 100.110 ± 0.940 for MON and FEX, respectively. Furthermore, the method was found to be eco‐friendly green as was evaluated according to the Green Analytical Procedure Index tool guidelines and analytical eco‐scale.

The Impact of Montelukast’s Black Box Warning on Pediatric Mental Health Adverse Event Reports

OBJECTIVE In March 2020, the US Food and Drug Administration (FDA) required a black box warning for montelukast due to serious mental health side effects. We hypothesized the warning would lead to an overall decrease in reports of mental health symptoms and disorders related to montelukast in both ­pre-adolescent and adolescent groups. METHODS Adverse events of pre-adolescent and adolescent children taking montelukast sodium were reviewed from March 1, 2018 to March 3, 2020 and March 4, 2020 to February 28, 2022 using the FDA’s Adverse Events Reporting System. The objective was to determine if mental health adverse event reports were influenced by placement of a Boxed Warning. Adverse reactions were grouped into 8 categories deemed to be related to mental health guided by the research team’s interpretation of the FDA Sentinel Report. Chi-square tests were used to compare time periods and reports of the mental health categories. RESULTS Of the 1570 reports assessed, 1295 (82.5%) included ≥1 mental health concern. Nine hundred ninety-six (84.2%) of the 1183 reports involving pre-adolescents and 299 (77.3%) of the 387 reports involving adolescents included ≥1 mental health reaction. Statistically significant changes for pre-adolescents were found in reports related to depression (χ2 (1) = 4.30, p = 0.044), and sleep (χ2 (1) = 5.74, p = 0.019), which both decreased between the pre and post periods. The only statistically significant change across categories for adolescents was a reduction in aggression reports between time periods (χ2 (1) = 8.5, p = 0.004). CONCLUSIONS After placement of an FDA black box warning on montelukast, total number of reports ­including mental health adverse events decreased in pre-adolescents; however, several categories ­assessed increased for adolescents.

Investigation into actions of Xiebai and Zengye decoction on cough sensitivity, airway inflammation and gut microbiota in the rat model of post-infectious cough

This work was undertaken to observe therapeutic effect of Xiebai and Zengye (XBZY) decoction on post-infectious cough (PIC) in rats, as well as its effect on gut microbiota and the exploration of the intestinal microecological mechanisms of XBZY decoction in the treatment of PIC. Using a random number table, the rats that were successfully modelled were assigned to the PIC, XBZY group (14.8 g/kg/d), and montelukast sodium treatment (MAS) group (1 mg/kg/d). The cough sensitivity of rats and changes in fecal water content were assessed, and serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) levels were determined by ELISA. The histopathological changes in the bronchus and colon tissues were observed under the microscope after hematoxylin-eosin staining. Short-chain fatty acids (SCFAs) in fecal samples were measured by gas chromatography, and changes in gut microbiota were observed using 16S rRNA sequencing. The PIC rats showed decreased fecal water content, increased cough sensitivity, elevated serum TNF-α and IL-8 levels, and higher bronchitis scores comparing to normal control group. The PIC rats showed reductions in SCFAs and significant changes in the structure of gut microbiota. XBZY decoction intervention led to increased fecal water content in rats, reduced cough sensitivity, decreased serum IL-8 and TNF-α levels, decreased bronchitis scores, and alleviated inflammatory cell infiltration was observed in the colonic mucosa. Additionally, elevated SCFAs levels were observed in the PIC rats. XBZY decoction intervention improved alpha-/beta-diversity, and corrected microbiota imbalance in PIC rats. SCFAs, TNF-α and IL-8, acetic acid was revealed to be positively associated with Allobaculum but inversely correlated with unclassified_f_Oscillospiraceae; propanoic acid was positively associated with Lactobacilli but negatively associated with Romboutsia; butanoic acid exhibited positive correlations with Akkermansia and Lactobacilli, but negative correlations with unclassified_f_Oscillospiraceae, Eubacterium_xylanophilum_group, and Lachnospiraceae_NK4A136_group; Additionally, TNF-α was inversely linked to Allobaculum, while IL-8 was positively related to Romboutsia and Turicibacter. In conclusion, XBZY decoction significantly reduced cough sensitivity and airway inflammation in PIC rats while ameliorating stool dryness and colonic inflammation. The protective effects of XBZY decoction could be linked to modulat gut microbiota in PIC rats, and regulat SCFAs contents in PIC rats, while the regulator mechanisms of XBZY decoction in gut microbiota still requires further in-depth investigation.

Assessing the Effectiveness of Montelukast Sodium in Managing Pulmonary Infections in Lung Cancer Patients

Objective: To investigate the efficacy of montelukast sodium in the treatment of lung cancer patients with pulmonary infections. Methods: A total of 330 patients diagnosed with lung cancer and pulmonary infection, who were admitted to the First Affiliated Hospital of Xi’an Medical University from 2020 to 2022, were selected as research subjects. They were randomly divided into two groups: a control group receiving conventional treatment and an observation group receiving conventional treatment combined with montelukast sodium. Each group consisted of 165 cases. The time required for clinical symptom improvement, the resolution of lung infection signs, and the levels of serum inflammatory factors before and after treatment were compared between the two groups. Results: The observation group exhibited significantly faster improvement in clinical symptoms compared to the control group (P &lt; 0.001). ELISA assays were conducted to detect the expression levels of IL-1β, IL-6, IL-8, and TNF-α in the serum of both groups at 1 week and 2 weeks into the treatment. The results indicated that, as the treatment progressed, the observation group displayed significantly lower levels of the four serum inflammatory factors compared to the control group (P &lt; 0.001). Conclusion: Montelukast sodium demonstrates efficacy in the treatment of patients with lung cancer complicated by pulmonary infections. These findings suggest its potential for further verification and clinical application.

IVIVC assessment, pharmacokinetic evaluation, and X-ray radiography mapping of Novel Parteck® SRP 80 and hypromellose-loaded LTD4 receptor antagonist chronosystem

BackgroundThe current research aims to determine the pharmacokinetic parameters, mucoadhesive strength, and IVIVC correlation of the novel chronotherapeutic drug delivery system of montelukast sodium (MTS) loaded Parteck® SRP80 and hypromellose system. To accomplish this, an HPLC method was developed which is highly sensitive, precise, and rapid for quantifying pure MTS in rabbit plasma. Mucoadhesive strength and time-dependent mobility of developed formulation were established by ex-vivo study and X-ray radiography, respectively. Using a fraction of drug absorbed (FDA) and a fraction of drug released (FDR), Level-A in-vitro in-vivo correlation (IVIVC) was developed. According to ICH Q1A (R2) standards, stability experiments were conducted for 180 days.ResultMTS retention time came as 3.971 min with a mobile phase of methanol: acetonitrile: 0.2 mM sodium acetate buffer (5:90:5). In-vitro dissolution showed pulsatile release of the drug up to 24 h with two lag phases. The in-vivo study showed a Cmax of 490.16 ± 33.95 ng/ml, Tmax of 9 h, and MRT of 14.08 ± 1.21 h. The correlation coefficient of 0.9899 confirmed the level-A IVIVC. Uncoated matrix tablet of Parteck® SRP 80 displayed mucoadhesive strength 1.25-fold higher than hypromellose. Stability experiments found no significant changes in drug content, physical appearance, and cumulative percentage release with a similarity factor of 87–90.ConclusionA single oral dose in-vivo study proved the sustained release of the drug for 24 h with satisfactory mucoadhesive strength. Moreover, X-ray radiography has confirmed the time-dependent presence of formulation at the needed spot. This study fulfilled all the requirements for chronotherapy of asthma and can be scaled up in the future.Graphical abstract

Effects of oral cysteine leukotriene receptor antagonist-montelukast on adenoid lymphoid tissue: a histopathological study under light microscope.

Background: Adenoidal hypertrophy (AH) is one of the most common causes of upper airway obstruction in children. Drug and surgical treatment are the typical treatment of AH. The study on the inflammatory mechanism of AH in children provides a new idea for preoperative intervention and non-surgical treatment with anti-inflammatory drugs such as montelukast sodium (a cysteine leukotriene receptor antagonist). The aim of this study is to evaluate the effect of montelukast sodium on adenoidal lymphoid tissue pathology in children with AH under light microscope. Objective: To study whether there is any change in pathology of the adenoidal lymphoid tissue under the light microscope compared with the control group in children with moderate to severe simple AH treated with montelukast sodium for 1month before operation. Materials and methods: Twenty patients (8 males, 12 females, 3-8 years old) with moderate to severe AH who were prepared for surgical treatment were selected. All the patients were examined by Nasopharyngeal CT and hemocyte analysis before operation. 20 subjects were randomly divided into two groups: One group was given montelukast chewable tablets 5mg/d, qn, for 4 weeks; The control group was given placebo 5mg/d, qn, for 4 weeks. After 4 weeks, the adenoids were removed and examined histopathology. Results: Compared with the control group, the number of lymphocytes in the blood cell analysis of the study group was significantly reduced, with a statistically significant difference (p < 0.05). And the number of germinal centers in adenoid tissue of the study group was relatively reduced, no small cyst was found in the epithelium, and the degree of inflammatory cell infiltration was reduced, with a statistically significant difference (p < 0.05). Conclusion: Montelukast can reduce the number of reactive cells, the number of lymphocytes in blood cells and blood vessels in adenoid lymphoid tissue, which can provide a new idea for preoperative intervention and non-surgical treatment of adenoid hypertrophy in children. However, this is only a pilot study and a longer treatment period is needed to assess the long-term effects of montelukast sodium on adenoid lymphoid tissue. Clinical Trial Registration: www.Chictr.org.cn, identifier ChiCTR2300075040.

Association of LOX gene G473A polymorphism with the occurrence of allergic rhinitis and efficacy of montelukast sodium in children

ABSTRACT Allergic rhinitis (AR) is very common in adolescents, and current treatment options are complex and unsatisfactory. The objective of this study was to analyze the association of lysyl oxidase (LOX) gene G473A polymorphism with susceptibility to AR in children. In addition, we analyzed the therapeutic effect of montelukast sodium on AR. Forty-five children with AR (research group, 8.16±2.88 years old) and 51 healthy children (control group, 8.22±3.87 years old) during the same period were selected. The LOX gene G473A polymorphism was detected with polymerase chain reaction (PCR)-restriction fragment length polymorphism method. The effect of G473A polymorphism in the occurrence of AR was assessed by logistic regression analysis. In addition, the levels of C-reactive protein (CRP), Interleukin (IL-6), and IL-8 were measured to observe the relationship between G473A polymorphism and inflammatory factors. Finally, montelukast sodium was given to children with AR to investigate the effect of G473A polymorphism on clinical outcomes. The number of G473A polymorphisms in the research group was not significantly different from the control group for GA-type (P = 0.521). However, the number of GG-type polymorphisms was less while the number of type AA was more than the control group (P = 0.044 and 0.046). Children carrying the AA gene had an approximately 4-fold increased risk of AR, while those carrying the GG gene had a decreased risk (P < 0.001). Moreover, children carrying the GG gene had lower levels of CRP, IL-6, and IL-8 and better clinical outcomes, while those carrying the AA gene had higher levels of inflammatory factors and worse outcomes (P<0.05). LOX gene G473A polymorphism is closely associated with AR pathogenesis and may have an important research value in antagonizing the therapeutic effect of montelukast sodium.

Functionalized ZIF‐8 with Aminopropyltrimethoxysilane as Montelukast Sodium Carrier for Medical Application

AbstractMontelukast sodium (MS) as an anti‐inflammatory agent in asthma requires a drug delivery system to sustain release at specific doses. ZIF‐8 commonly used in drug delivery systems due to its low cytotoxicity and biodegradability was functionalized with 3‐aminopropyltrimethoxysilane (APTES) as a carrier (ZIF‐8@APTES) for MS. The particles were characterized with Field emission scanning electron microscopy (FE‐SEM), Fourier transform infrared (FTIR), X‐ray diffraction (XRD), Brunauer‐Emmett‐Teller (BET) method, and thermogravimetric analysis (TGA). Furthermore, the biocompatibility of ZIF‐8@APTES‐MS on a normal murine cell line (L929) and its antioxidant activity were investigated. The results showed that MS was gradually released from ZIF‐8@APTES‐MS in phosphate buffer solution (pH 7.4) over 6 hours. ZIF‐8@APTES and ZIF‐8@APTES‐MS also had good biocompatibility properties, and significantly (P≤0.05) enhanced total antioxidant activity at high doses (32 μg/mL). In conclusion ZIF‐8@APTES‐MS can be a promising drug delivery system for MS.