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International Immunopharmacology Dec 2023Montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, is emerging as an attractive strategy to curtail diabetic complications; however, its role in aortic...
AIMS
Montelukast, a cysteinyl leukotriene receptor (CysLTR)1 antagonist, is emerging as an attractive strategy to curtail diabetic complications; however, its role in aortic and testicular tissues is unknown. This study investigated the effect of CysLTR1 antagonism by montelukast on toll-like receptor (TLR)4 and nuclear factor kappa B (NF-κB) pathways in diabetes-induced aortic and testicular injury.
METHODS
Adult male Sprague-Dawley rats were made diabetic with Streptozotocin (STZ, 55 mg/kg). Following this, Streptozotocin-induced diabetic (SD) rats were administered montelukast (10 and 20 mg/kg, orally) for 8 weeks. Blood glucose, serum malondialdehyde (MDA), inflammatory markers, and histopathology were evaluated.
RESULTS
Montelukast showed protection against diabetic complications, as evidenced by the ameliorative effect against STZ-induced alterations in oxidative stress as indicated by serum MDA levels. Moreover, montelukast conferred a significant decrease in the aortic and testicular levels of CysLTR1, TLR4, and NF-κB with a subsequent decrease in the levels of NOD-like receptor family pyrin domain containing (NLRP)3, caspase 1, interleukin (IL)-1β, IL-6, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α. Additionally, administration of montelukast resulted in autophagy stimulation, as shown by decreased p62/Sequestosome (SQSTM)1 levels. Finally, montelukast protection resulted in normal thickness of whole aortic wall, regular tunica (t.) intima, mild vacuolation of smooth muscle fibers in aorta, increased size of seminiferous tubules, and increased spermatogenesis in testis as demonstrated by histopathology.
CONCLUSIONS
The protective effect of montelukast against diabetes-induced aortic and testicular injury is due to its antioxidant, anti-inflammatory, and autophagy stimulation characteristics.
Topics: Rats; Male; Animals; NF-kappa B; Rats, Sprague-Dawley; Streptozocin; Diabetes Mellitus; Tumor Necrosis Factor-alpha; Inflammation; Diabetes Complications; Aorta
PubMed: 37907048
DOI: 10.1016/j.intimp.2023.111127 -
Drug Design, Development and Therapy 2021The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The aim of this study was to assess and compare the pharmacokinetic (PK) properties and bioequivalence of montelukast sodium chewable tablets prepared by two different manufacturers in healthy Chinese volunteers to obtain adequate PK evidence for the registration approval of the test formulation.
PATIENTS AND METHODS
A randomized-sequence, single-dose, open-label, 2-period crossover study was conducted in fasted and fed healthy Chinese volunteers (Chinese Clinical Trials Registry identifier: CTR20182362). Eighteen subjects each were selected for a fasted study and a fed study. Eligible participants were randomly assigned in a 1:1 ratio to receive a single dose of the reference formulation or the test formulation, followed by a 5-day washout period and the administration of the alternate formulation. Plasma samples were collected over a 24-hour period following tablet administration and analyzed for montelukast contents by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The PK parameters, such as maximum serum concentration (C), area under the curve (AUC) from t = 0 to the last quantifiable concentration (AUC), AUC from t = 0 to infinity (AUC), half-life (t), time to C (T), and terminal elimination rate constant (λ), were evaluated. The safety assessment included changes in vital signs (blood pressure, pulse, and temperature) or laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis) and the incidence of adverse events (AEs).
RESULTS
The geometric mean ratios (GMRs) between the two formulations for the primary pharmacokinetic parameters (C, AUC, and AUC ) and the corresponding 90% confidence intervals (Cis) were all within the range of 80.00-125.00% for both the fasting and fed states. The safety profiles for both treatments were comparable.
CONCLUSION
The PK analysis revealed that the test and reference formulations of montelukast sodium chewable tablets were bioequivalent and well-tolerated by healthy Chinese subjects.
Topics: Acetates; Administration, Oral; Adolescent; Adult; Asian People; Cross-Over Studies; Cyclopropanes; Drug Compounding; Fasting; Female; Healthy Volunteers; Humans; Male; Middle Aged; Quinolines; Sulfides; Tablets; Therapeutic Equivalency; Young Adult
PubMed: 33727797
DOI: 10.2147/DDDT.S298355 -
Nigerian Journal of Clinical Practice Apr 2023The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology.
BACKGROUND
The leukotriene D4 receptors have been detected in human bladder detrusor myocytes, and they can play the role of interstitial cystitis etiology.
AIM
Our study aims to explain the role of mast cells histologically and immunohistochemically in the pathogenesis and the effectiveness of montelukast that leukotriene D4 receptor antagonist in the treatment of interstitial cystitis.
SUBJECTS AND METHODS
Twenty-four Wistar albino adult female rats were used. Group 1 (n = 8): control (sham) group, Group 2 (n = 8): interstitial cystitis group, and Group 3 (n = 8): treatment group. Groups 2 and 3 rats were administered 75 mg/kg cyclophosphamide four times every three days intraperitoneally. The rats in the treatment group were started on montelukast sodium as 10 mg/kg, 1 × 1/day per orally after the last administration of cyclophosphamide and were given for 14 days. Mast cells in the bladder tissues were examined histologically, and the presence of IL-6, 8, VEGF, and TNF alpha was examined immunohistochemically.
RESULTS
Thin transitional epithelium, loose connective tissue, weak smooth muscle bundles, and signs of chronic inflammation were observed in the interstitial cystitis group. Regenerated transitional epithelium, intact basement membrane, compact lamina propia, thick smooth muscle bundles, and rare inflammatory cells were observed after the treatment with the montelukast. Mast cells were decreased in bladder tissue after treatment. IL-6, IL-8, VEGF, and TNF alpha levels were significantly decreased after treatment.
CONCLUSIONS
We found that inflammatory mediators were significantly reduced after treatment with montelukast in the interstitial cystitis group. Montelukast can be used as an effective drug in the treatment of interstitial cystitis.
Topics: Humans; Female; Rats; Animals; Cystitis, Interstitial; Vascular Endothelial Growth Factor A; Interleukin-6; Tumor Necrosis Factor-alpha; Rats, Wistar; Leukotriene Antagonists; Cyclophosphamide
PubMed: 37203102
DOI: 10.4103/njcp.njcp_385_22 -
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 -
Eye (London, England) May 2022Vernal keratoconjunctivitis is a chronic, seasonally exacerbated, allergic inflammation of the eye. The study aims to evaluate the efficacy and safety of oral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Vernal keratoconjunctivitis is a chronic, seasonally exacerbated, allergic inflammation of the eye. The study aims to evaluate the efficacy and safety of oral montelukast in treating vernal keratoconjunctivitis in pediatric patients.
METHODS
This is a 26-week, prospective, randomized, open-label study. Fifty-eight patients were randomly assigned to two groups-the treatment (montelukast) and control groups. At the beginning of the study, both the groups received topical loteprednol etabonate (0.1%) in tapering doses for a month, and topical olopatadine (0.1%) for the first 3 months. Symptoms and signs observed before and after treatment and assigned scores were studied. The primary efficacy endpoint was change in the mean score on the visual analog scale (VAS) for each subjective symptom. The secondary efficacy endpoint was change in the total score of objective signs.
RESULTS
The montelukast group showed clinically relevant improvements in the signs and symptoms of vernal keratoconjunctivitis, compared to the control group. There was considerable improvement in clinical signs. Individual symptoms such as redness, itching, foreign body sensation, and tearing showed significant improvement at 6 months follow-up. The gradual improvement in symptoms until the last visit was statistically more significant within montelukast group. Mean VAS score showed statistically significant improvement in itching (p < 0.001) and redness (p < 0.008) in montelukast group even at 3 months. No adverse events were reported in either group.
CONCLUSIONS
Montelukast was found to be safe and effective as a long-term therapy to prevent relapse in moderate to severe vernal keratoconjunctivitis.
Topics: Acetates; Child; Conjunctivitis, Allergic; Cyclopropanes; Humans; Ophthalmic Solutions; Prospective Studies; Pruritus; Quinolines; Seasons; Sulfides; Treatment Outcome
PubMed: 33947979
DOI: 10.1038/s41433-021-01484-3 -
Journal of Analytical Methods in... 2021In this study, we present a new, green electrochemical method for potentiometric estimation of desloratadine and montelukast sodium in their pure and binary dosage form....
In this study, we present a new, green electrochemical method for potentiometric estimation of desloratadine and montelukast sodium in their pure and binary dosage form. For that, three pencil graphite sensors were fabricated; the first one was prepared to analyse desloratadine drug (DES) by coating the graphite bar with the coating membrane, which comprises the ion pair of desloratadine and ammonium reineckate reagent (RNK), the polymer poly vinyl chloride (PVC), and the plasticizers dibutyl phthalate (DBP). The second one, which was used to analyse montelukast (MON), was constructed by using the ion pair of cadmium chloride reagent (Cd.) with montelukast and the same earlier named polymer and plasticizer. As a trial to analyse both of the drugs by the same sensor consecutively, we have constructed a combined pencil graphite electrode, which contains the two earlier suggested ion pairs, that is, we can use this electrode to selectively analyse for each drug. The proposed electrodes were effectively used for analysis of DES and MON as a single dosage form and as combined pharmaceutical preparation, without any need for prior separation that was performed depending on the difference in the efficient pH range for each sensor. The proposed sensors exhibited a Nernstian equation slopes of -30.11, 27.70, (-29.16, 29.79) mv. decade in the linearity range 5.00 × 10-1.00 × 10 and 1.00 × 10 - 1.00 × 10 M, respectively. The sensors exhibit high sensitivity according to LOD values ((0.036-0.018) - (0.025-0.026) M), respectively, and important selectivity toward the studied drugs in presence of interfering ions and excipients. The optimum circumstances were studied, and the method was validated by application of ICH rules. Finally, the method was compared with a documented method, and the required statistical values were calculated.
PubMed: 34035974
DOI: 10.1155/2021/5540907 -
Annals of Translational Medicine Jan 2023The oral soluble film (OSF) is a new drug delivery system. Whether montelukast sodium OSF has similar pharmacokinetic (PK) properties and bioequivalence to chewable...
Pharmacokinetics and bioequivalence study of montelukast sodium oral soluble film and chewable tablet in healthy Chinese volunteers: randomized trials under fasting and fed conditions.
BACKGROUND
The oral soluble film (OSF) is a new drug delivery system. Whether montelukast sodium OSF has similar pharmacokinetic (PK) properties and bioequivalence to chewable tablet (CT) should be investigated.
METHODS
This study, conducted at Haikou People's Hospital, consisted of two trials: a randomized, open-label, single-dose, 3-sequence, 3-period crossover trial under fasting conditions and a randomized, open-label, single-dose, 2-sequence, 2-period crossover trial under fed conditions. Healthy volunteers were randomized 1:1:1 to receive single-dose oral montelukast sodium OSF without water, OSF, or CT with water in the fasting trial, and 1:1 to receive OSF or CT with water in the fed trial in each period, with a 7-day washout period. Randomization was performed according to random number tables generated using computer. Blood samples were collected over a 24-h period. Plasma drug concentrations were tested using high-performance liquid chromatography-tandem mass spectrometry. The primary PK parameters were maximum plasma drug concentration (C), area under the plasma drug concentration-time curve (AUC) from t=0 to the last quantifiable concentration (AUC), and AUC from t=0 to infinity (AUC). The other PK parameters included time to C (T), terminal elimination rate constant (λ), and half-life (t). Safety was also assessed. Analysis of variance on log-transformed primary PK parameters was applied to analyze the bioequivalence between the OSF and CT. The bioequivalence margin was 80-125%.
RESULTS
From November 2018 to January 2019, 30 subjects were included in each trial. The PK parameters between OSF and CT were numerically similar. All 90% confidence intervals (CIs) of the geometric mean ratio (GMR) for the primary PK parameters fell within 80-125%, confirming the bioequivalence of montelukast sodium OSF and CT under fasting and fed conditions. In the fasting trial, 6 (20%) adverse events (AEs) were reported, including 3 (10%) cases after OSF administration without water and 3 (10%) after OSF administration with water, with no serious AEs. No AEs were recorded in the fed trial.
CONCLUSIONS
Montelukast sodium OSF is bioequivalent to CT, with acceptable safety. The OSF is an alternative option of CT.
TRIAL REGISTRATION
ClinicalTrials.gov identifiers: NCT05528198 (the fasting trial) and NCT05531994 (the fed trial).
PubMed: 36819512
DOI: 10.21037/atm-22-6485 -
Molecular Medicine Reports Aug 2018Osteoclasts (OCs) are resorptive cells responsible for bone erosion in diseases, including osteoporosis, periodontitis and rheumatoid arthritis. Montelukast is a...
Osteoclasts (OCs) are resorptive cells responsible for bone erosion in diseases, including osteoporosis, periodontitis and rheumatoid arthritis. Montelukast is a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist clinically used for the treatment of asthma. In the present study, the role of CysLTR1 on OC formation and bone loss was investigated using montelukast. Montelukast inhibited receptor activator of nuclear factor‑κB ligand (RANKL)‑induced OC formation in cultures of mouse bone marrow macrophages. Additionally, montelukast suppressed actin ring formation and bone resorption activity of differentiated OCs. The inhibitory effect of montelukast was associated with impaired activation of extracellular signal‑regulated kinase, AKT serine/threonine kinase, and/or phospholipase Cγ2 signaling pathways downstream of RANK, followed by decreased expression of nuclear factor of activated T cells c1. Notably, OC formation was efficiently restored by addition of adenosine diphosphate, a P2Y12 agonist, as well as by addition of CysLT. Furthermore, similar to montelukast, P2Y12 blockade by a pharmacological inhibitor or siRNAs suppressed OC differentiation. These data indicate the involvement of the P2Y12 receptor in the inhibitory effect of montelukast on osteoclastogenesis. In vivo, montelukast significantly inhibited inflammation‑induced osteoclastogenesis in the calvarial model. Montelukast also served a protective role in a murine ovariectomy (OVX)‑ and unloading‑induced bone loss model. Altogether, these results confirmed that the CysLTR1 antagonist exerted an inhibitory effect on OC formation in vitro and in vivo. It may be useful for the treatment of bone diseases associated with excessive bone resorption.
Topics: Acetates; Animals; Bone Marrow Cells; Bone Resorption; Cell Differentiation; Cyclopropanes; Humans; Macrophages; Mice; Osteoclasts; Ovariectomy; Quinolines; RANK Ligand; Receptors, Leukotriene; Receptors, Purinergic P2Y12; Signal Transduction; Sulfides
PubMed: 29916540
DOI: 10.3892/mmr.2018.9179 -
Irish Journal of Medical Science Aug 2020Asthma in elderly patients causes excessive suffering and inconvenience. Regimens with better efficacy and less adverse events are still in need of researches.
BACKGROUND
Asthma in elderly patients causes excessive suffering and inconvenience. Regimens with better efficacy and less adverse events are still in need of researches.
AIMS
To investigate the effect of montelukast sodium plus budesonide on lung function, inflammatory factors, and immune levels in elderly asthma patients.
METHODS
A total of 180 patients with asthma were assigned into the control group and the observation group. The control group was given aerosol inhalation of budesonide suspension, while the observation group was given budesonide inhalation and oral montelukast sodium. The treatment effect, lung function (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF)%), inflammatory factors (interleukin (IL)-4, IL-6, and tumor necrosis factor-α (TNF-α)), and immune level (immunoglobulin (Ig) A, and IgE) were analyzed and compared between the two groups.
RESULTS
After treatment, the effective rate was significantly higher in the observation group. The lung function and serum inflammatory factors were improved in both groups. The FEV1, FVC, and PEF% in the observation group were better, and the inflammatory factors IL-4, IL-6, and TNF-α were lower. Patients in both groups showed elevated IgA level and reduced IgE level, and the improvements were more significant in the observation group. There was no significant difference between the two groups in terms of adverse reaction.
CONCLUSIONS
Montelukast sodium plus budesonide has a promising clinical effect on asthma in elderly patients, effectively improves lung function and immunocompetence, and controls inflammatory response, without increasing the adverse reaction.
Topics: Acetates; Aged; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Budesonide; Cyclopropanes; Female; Humans; Inflammation; Male; Middle Aged; Quinolines; Respiratory Function Tests; Sulfides
PubMed: 31900843
DOI: 10.1007/s11845-019-02167-5 -
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