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This study investigates the pharmacokinetics (PK) of montelukast (MTK), a cysteinyl leukotriene receptor antagonist increasingly being considered in veterinary medicine. In dogs, MTK has found indications mainly for treating atopic dermatitis as an off-label use. Six male Labrador dogs underwent a single oral administration of MTK (40â¯mg/dog) in both fasted and fed conditions according to an open, single-dose, two-treatment, two-phase, cross-over design, with a washout period of one week. Blood was withdrawn to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24â¯hr. MTK plasma concentrations were quantified using a validated HPLC method, and the data were analysed using PKanalix™ software with a non-compartmental approach. Concentrations remained quantifiable at 24â¯hr after administration, under both conditions. No significant differences were observed in the PK parameters between the fasted and fed states. MTK was relatively eliminated slowly, with t1/2 values of 8.10 and 7.68â¯hr after fasted and fed states, respectively. The attainment of maximum concentration (Cmax) occurred at a Tmax of 4â¯hr, with mean values of 1.98⯵g/mL and 2.80⯵g/mL under fasted and fed conditions, respectively. Given the unknown therapeutic range of MTK in dogs and the absence of controlled studies proving its efficacy in this species, further dosing adjustments and refinements should be considered based on both the current PK data and the need to establish an effective therapeutic range, if present. Future research should focus on efficacy studies, multiple-dose investigations, and pharmacodynamic assessments to evaluate the suitability of MTK use in dogs.
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This systematic review and meta-analysis evaluated the safety of montelukast in treating asthma during pregnancy, focusing on maternal and fetal outcomes such as congenital anomalies (CA), preterm delivery, low birthweight, spontaneous abortion, gestational diabetes mellitus, and preeclampsia. A comprehensive literature search was conducted in Google Scholar, PubMed, and the Cochrane Library databases from inception until April 30, 2024. The eligible studies assessed the safety of montelukast for asthma treatment during pregnancy. The review suggests that montelukast use during pregnancy may not significantly increase the risk of major CA. The pooled results yielded risk ratio (RR) for CA was 1.13 [95% CI (0.74, 1.73), p = 0.56, I2 = 0%]. Montelukast may be associated with preterm delivery and a low birthweight odds ratio (OR) of 1.82 [95% CI (1.35, 2.45), p < 0.001, I2 = 0%]. No significant risks were found concerning neurodevelopmental outcomes. The associations with spontaneous abortion were inconclusive [OR = 1.03, 95% CI (0.72, 1.5), p = 0.86, I2 = 73%], highlighting the need for further research. This comprehensive review underscores the importance of further investigating the safety profile of montelukast during pregnancy. While the overall findings indicate a relatively favorable safety profile, especially regarding major CA, careful consideration is needed for the potential risks of preterm delivery and low birthweight.
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The development of sustainable analytical methodologies that minimize hazards, waste generation, and energy consumption has become crucial. This study introduces pioneering greenâblue-white approaches for the simultaneous quantification of montelukast sodium (MLK) and fexofenadine hydrochloride (FEX) in combination formulations. The first approach employs an ultra-performance liquid chromatographic method (UPLC) with a green micellar mobile phase of 0.02 M sodium dodecyl sulfate and 10% 1-pentanol (65:35%). The method demonstrated excellent resolution, peak symmetry, and a short analysis time, with retention times of 3.53 min for MLK and 1.67 min for FEX. The MLK and FEX linearities were 1-260 and 1.2-312 µg/mL, respectively. The second approach involves complementary built-in spectroscopic techniques (second derivative, third derivative, and ratio difference methods) using water as a solvent, providing a green, simple, low-cost alternative in laboratories where expensive chromatographic devices may not be readily available. The MLK and FEX linearities were 3-50 and 3-60 µg/mL, respectively. All methods were comprehensively validated and showed satisfactory results. The proposed methods demonstrated excellent linearity (r2 ≥ 0.9990), accuracy (recovery 98.5-101.5%), and precision (RSD ≤ 2%) across wide concentration ranges. A multifaceted evaluation was conducted to assess the environmental sustainability, real-world applicability, and economic viability of the proposed methods in comparison with previously reported techniques. This comprehensive assessment leveraged several state-of-the-art tools, including NEMI, ComplexGAPI, AGREE, ESA, BAGI, and RGB12. The suggested approaches exhibited favorable quadrant profiles in the NEMI and ComplexGAPI assessments, coupled with higher AGREE scores (0.90, 0.86) than reported (0.62, 0.74, 0.75, 0.69, 0.74, 0.74, and 0.75), in addition to higher ESA score (88, 92) than reported (75, 84, 85, 79, 82, 82, and 83), collectively affirming their environmentally friendly credentials. Moreover, we embraced the innovative notions of 'blueness' and 'whiteness' assessment by harnessing the recently formulated BAGI and RGB12 algorithms. The higher BAGI score (90, 82.5) than reported (72.5, 70, 70, 67.5, 67.5, 67.5, and 72.5), confirmed the excellent real-world applicability of the proposed methods, while the notable RGB12 indices (89.8, 88.1) than reported (67.8, 72.8, 71.5, 67.1, 73.7, 70.3, and 73.2), validated their cost-effectiveness and overall sustainability, contributing to an eco-friendly future for quality control processes.
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Morbihan's disease is a rare condition characterized by chronic facial edema. While its exact cause is unknown, it is thought to involve local cutaneous vascularization and lymphatic drainage imbalance. Traditional treatment options are often ineffective, and no established efficient treatment exists. We present a case study of a 17-year-old male with Morbihan's syndrome who showed resistance to traditional treatments but responded well to a combination of cromolyn sodium nasal spray and oral montelukast after histopathology revealed hyperplasia of plasma cells and mast cells. This combination has not been used before for Morbihan's syndrome. Our review of the literature also provides insight for clinicians seeking to manage this condition.
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BACKGROUND: Dengue fever continues to pose significant health challenges globally, with recent outbreaks in Bihar, India, prompting a search for effective therapeutic interventions. This study assesses the effectiveness of Montelukast, traditionally used for asthma, in mitigating the severity of dengue fever symptoms and its progression to dengue shock syndrome (DSS). OBJECTIVE: To evaluate the impact of Montelukast on the prevalence of dengue warning signs and the incidence of DSS in adult patients. METHODS: A prospective observational study was conducted at the Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, India, from August 2022 to October 2023, enrolling 500 patients diagnosed with dengue fever. Participants were divided into two groups. About 250 were treated with Montelukast and 250 received standard care. Outcomes measured included the incidence of warning signs, DSS, length of hospital stay, and 30-day mortality. RESULTS: The Montelukast group exhibited a 24% lower prevalence of dengue warning signs compared to the control group, with 90 out of 250 patients (36%) in the Montelukast group versus 150 out of 250 patients (60%) in the control group (p < 0.001). The incidence of DSS was significantly reduced in the Montelukast group, with 4 out of 250 patients (1.6%) compared to 21 out of 250 patients (8.4%) in the control group (odds ratio: 0.178, p < 0.001). Furthermore, Montelukast users experienced shorter hospital stays (average 4.52 days vs. 6.54 days, T-statistic: -7.59, p = 1.58×10-13) and a reduced 30-day mortality rate, with 5 out of 250 patients (2%) in the Montelukast group versus 12 out of 250 patients (5%) in the control group (p < 0.03). CONCLUSION: Montelukast significantly lowers the incidence of dengue warning signs and DSS, shortens hospital stays, and decreases mortality rates among dengue patients, supporting its potential integration into existing dengue treatment protocols. This study highlights the need for further clinical trials to confirm these findings and fully understand the therapeutic mechanisms of Montelukast in dengue management.
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Cholangiocarcinoma (CCA) is a cancer with a poor prognosis due to difficulties in diagnosis and limited treatment options, highlighting the urgent need for new targeted therapies. In a clinical setting, we found that leukotriene levels in bile were higher than in serum. Immunohistochemical analysis of surgically resected samples also revealed that CysLT receptor 1 (CysLTR1) was more highly expressed in CCA than in normal bile duct tissue, prompting us to investigate leukotriene as a potential therapeutic target in CCA. In vitro studies using CCA cell lines expressing CysLTR1 showed that leukotriene D4, a major ligand of CysLTR1, promoted cell proliferation, with increased phosphorylation of AKT and extracellular signal-regulated kinase 1/2 (ERK1/2). Additionally, treatment with two clinically available anti-allergic drugs-zileuton, an inhibitor of CysLT formation, and montelukast, a CysLTR1 inhibitor-had inhibitory effects on cell proliferation and migratory capacity, accompanied by the reduced phosphorylation of AKT and ERK1/2. Furthermore, the simultaneous administration of both drugs synergistically enhanced the inhibitory effect on cell proliferation. Our study suggests that use of these drugs may represent a novel approach to treat CCA through drug repositioning.
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Neoplasias de los Conductos Biliares , Proliferación Celular , Colangiocarcinoma , Hidroxiurea , Antagonistas de Leucotrieno , Quinolinas , Receptores de Leucotrienos , Sulfuros , Humanos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Proliferación Celular/efectos de los fármacos , Receptores de Leucotrienos/metabolismo , Antagonistas de Leucotrieno/farmacología , Antagonistas de Leucotrieno/uso terapéutico , Línea Celular Tumoral , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Sulfuros/farmacología , Quinolinas/farmacología , Hidroxiurea/análogos & derivados , Hidroxiurea/farmacología , Hidroxiurea/uso terapéutico , Acetatos/farmacología , Acetatos/química , Masculino , Ciclopropanos/farmacología , Ciclopropanos/uso terapéutico , Movimiento Celular/efectos de los fármacos , Femenino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-akt/metabolismo , Progresión de la Enfermedad , Leucotrienos/metabolismo , Fosforilación/efectos de los fármacos , Anciano , Leucotrieno D4/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacosRESUMEN
The purpose of this study was to enhance the stability of montelukast and levocetirizine for the development of a fixed-dose combination (FDC) monolayer tablet. To evaluate the compatibility of montelukast and levocetirizine, a mixture of the two drugs was prepared, and changes in the appearance characteristics and impurity content were observed in a dry oven at 60 °C. Excipients that contributed minimally to impurity increases were selected to minimize drug interactions. Mannitol, microcrystalline cellulose, croscarmellose sodium, hypromellose, and sodium citrate were chosen as excipients, and montelukast-levocetirizine FDC monolayer tablets were prepared by wet granulating the two drugs separately. A separate granulation of montelukast and levocetirizine, along with the addition of sodium citrate as a pH stabilizer, minimized the changes in tablet appearance and impurity levels. The prepared tablets demonstrated release profiles equivalent to those of commercial products in comparative dissolution tests. Subsequent stability testing at 40 ± 2 °C and 75 ± 5% RH for 6 months confirmed that the drug content, dissolution rate, and impurity content met the specified acceptance criteria. In conclusion, the montelukast-levocetirizine FDC monolayer tablet developed in this study offers a potential alternative to commercial products.
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BACKGROUNDS & AIM: Placental insufficiency is a serious complication that affects pregnancy and fetal growth. Cyclophosphamide (CYC) is considered one of the chemotherapeutic agents. Unfortunately, CYC not only affects tumor cells but also affects healthy cells causing multiple injuries including the placenta. The present study aimed to evaluate the effect of cysteinyl leukotriene receptor antagonist; montelukast (MK), on CYC-induced placental injury in rats. MATERIALS AND METHODS: Forty-eight female Wister rats were randomly divided into 8 experimental groups. Group 1: control pregnant group; Group 2: MK 5 mg-treated pregnant rats; Group 3: MK 10 mg-treated pregnant rats; Group 4: MK 20 mg-treated pregnant rats; Group 5: pregnant rats received CYC (20 mg/kg, i.p); Group 6: pregnant rats received MK 5 mg and CYC; Group 7: pregnant rats received MK 10 mg and CYC; Group 8: pregnant rats received MK 20 mg and CYC. Placental malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), placental growth factor (PlGF), and Nod-like receptor p3 (NLRP3) inflammasome were measured. Histological changes, interleukin-1ß (IL-1ß), and cleaved caspase-3 immuno-expressions were also evaluated. RESULTS: CYC showed a significant decrease in placental GSH, TAC, and PlGF with a significant increase in placental MDA, NLRP3, and immuno-expression of IL-1ß and caspase-3. MK showed significant improvement in all oxidative stress (MDA, GSH and TAC), inflammatory (NLRP3 and IL-1ß), and apoptotic (caspase-3) parameters. CONCLUSION: According to the findings, MK was proved to have a possible protective role in CYC-induced placental injury via modulation of NLRP3/IL-1ß signaling pathway with anti-oxidant, anti-inflammatory, and anti-apoptotic effects.
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Acetatos , Ciclofosfamida , Ciclopropanos , Interleucina-1beta , Antagonistas de Leucotrieno , Proteína con Dominio Pirina 3 de la Familia NLR , Placenta , Quinolinas , Ratas Wistar , Transducción de Señal , Sulfuros , Animales , Femenino , Embarazo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Ciclofosfamida/toxicidad , Ciclofosfamida/efectos adversos , Quinolinas/farmacología , Quinolinas/uso terapéutico , Acetatos/uso terapéutico , Acetatos/farmacología , Interleucina-1beta/metabolismo , Placenta/efectos de los fármacos , Placenta/patología , Placenta/metabolismo , Antagonistas de Leucotrieno/farmacología , Antagonistas de Leucotrieno/uso terapéutico , Transducción de Señal/efectos de los fármacos , Ratas , Factor de Crecimiento Placentario/metabolismo , Estrés Oxidativo/efectos de los fármacos , Inflamasomas/metabolismo , Apoptosis/efectos de los fármacosRESUMEN
Introduction: Kidney damage can result from various factors, leading to structural and functional changes in the kidney. Acute kidney injury (AKI) refers to a sudden decline in kidney function, while chronic kidney disease involves a gradual deterioration lasting more than 3 months. Mechanisms of renal injury include impaired microcirculation, inflammation, and oxidative stress. Cysteinyl-leukotrienes (CysLTs) are inflammatory substances contributing to tissue damage. Montelukast, a leukotriene receptor antagonist, has shown potential renoprotective effects in experimental models of kidney injury. Methods: The authors conducted a scoping review using PubMed, Scopus, and Web of Science databases to identify relevant studies investigating the impact of montelukast on renal diseases. Articles published until 2022 were included and evaluated for quality. Data extraction and analysis were performed based on predetermined inclusion criteria. Results: The scoping review included 30 studies from 8 countries. Montelukast demonstrated therapeutic effects in various experimental models of nephrotoxicity and AKI induced by agents such as cisplatin, lipopolysaccharide, diclofenac, amikacin, Escherichia coli, cyclosporine, methotrexate, cobalt-60 gamma radiation, doxorubicin, and cadmium. Studies involving human subjects with nephrotic syndrome, pyelonephritis, and other renal diseases also reported positive outcomes with montelukast treatment. Montelukast exhibited anti-inflammatory, anti-apoptotic, antioxidant, and neutrophil-inhibiting properties, leading to improved kidney function and histopathological changes. Conclusions: Montelukast shows promise as a renoprotective medication, particularly in early-stage kidney injury. Its ability to mitigate inflammation, oxidative stress, and neutrophil infiltration contributes to its therapeutic effects. Further research is needed to explore the clinical applications and mechanisms underlying the renoprotective action of montelukast.
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BACKGROUND: Capsular contracture (CC) remains a very common complication and the main cause of reoperation following a mammary implant surgery. Leukotrienes play an important role in the inflammatory cascade linked to the development of the periprosthetic capsule. The aim of this paper is to evaluate the incidence of recurrence of capsular contracture in female patients who underwent a secondary mammary augmentation due to this etiology, with and without treatment with leukotriene inhibitors during postoperative care. MATERIAL AND METHODS: Sixty-four women submitted to a secondary mammary augmentation due to CC were evaluated retrospectively. Out of these patients, 20 (31%) were treated with Montelukast for 3 months. The remaining 44 (69%) did not receive antileukotriene. The presence of capsular contracture was measured using the Baker classification and magnetic resonance imaging a year after postoperative care. The median follow-up period was 15 months. RESULTS: The patients receiving Montelukast (n = 20) presented a 15% CC rate (n = 1). The women that did not receive antileukotriene therapy (n = 44) presented a 16% CC rate (n = 7). CONCLUSION: The results of our study show that treatment with Montelukast for 3 months after the operation is associated with lower rates of capsular contracture when compared to patients that did not receive the treatment. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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INTRODUCTION: The objective of the reported work was to develop Montelukast sodium (MS) solid lipid nanoparticles (MS-SLNs) to ameliorate its oral bio-absorption. Herein, the highpressure homogenization (HPH) principle was utilized for the fabrication of MS-SLNs. METHOD: The study encompasses a 23 full factorial statistical design approach where mean particle size (Y1) and percent entrapment efficiency (Y2) were screened as dependent variables while, the concentration of lipid (X1), surfactant (X2), and co-surfactant (X3) were screened as independent variables. The investigation of MS-SLNs by DSC and XRD studies unveiled the molecular dispersion of MS into the SLNs while TEM study showed the smooth surface of developed MSSLNs. The optimized MS-SLNs exhibited mean particle size (MPS) = 115.5 ± 1.27 nm, polydispersity index (PDI) = 0.256 ± 0.04, zeta potential (ζ) = -21.9 ± 0.32 mV and entrapment efficiency (EE) = 90.97 ± 1.12 %. The In vivo pharmacokinetic study performed in Albino Wistar rats revealed 2.87-fold increments in oral bioavailability. RESULTS: The accelerated stability studies of optimized formulation showed good physical and chemical stability. The shelf life estimated for the developed MS-SLN was found to be 22.38 months. CONCLUSION: At the outset, the developed MS-SLNs formulation showed a significant increment in oral bioavailability and also exhibited excellent stability in exaggerated storage conditions.
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Schistosomiasis remains the most devastating neglected tropical disease, affecting over 240 million people world-wide. The disease is caused by the eggs laid by mature female worms that are trapped in host's tissues, resulting in chronic Th2 driven fibrogranulmatous pathology. Although the disease can be treated with a relatively inexpensive drug, praziquantel (PZQ), re-infections remain a major problem in endemic areas. There is a need for new therapeutic drugs and alternative drug treatments for schistosomiasis. The current study hypothesized that cysteinyl leukotrienes (cysLTs) could mediate fibroproliferative pathology during schistosomiasis. Cysteinyl leukotrienes (cysLTs) are potent lipid mediators that are known to be key players in inflammatory diseases, such as asthma and allergic rhinitis. The present study aimed to investigate the role of cysLTR1 during experimental acute and chronic schistosomiasis using cysLTR1-/- mice, as well as the use of cysLTR1 inhibitor (Montelukast) to assess immune responses during chronic Schistosoma mansoni infection. Mice deficient of cysLTR1 and littermate control mice were infected with either high or low dose of Schistosoma mansoni to achieve chronic or acute schistosomiasis, respectively. Hepatic granulomatous inflammation, hepatic fibrosis and IL-4 production in the liver was significantly reduced in mice lacking cysLTR1 during chronic schistosomiasis, while reduced liver pathology was observed during acute schistosomiasis. Pharmacological blockade of cysLTR1 using montelukast in combination with PZQ reduced hepatic inflammation and parasite egg burden in chronically infected mice. Combination therapy led to the expansion of Tregs in chronically infected mice. We show that the disruption of cysLTR1 is dispensable for host survival during schistosomiasis, suggesting an important role cysLTR1 may play during early immunity against schistosomiasis. Our findings revealed that the combination of montelukast and PZQ could be a potential prophylactic treatment for chronic schistosomiasis by reducing fibrogranulomatous pathology in mice. In conclusion, the present study demonstrated that cysLTR1 is a potential target for host-directed therapy to ameliorate fibrogranulomatous pathology in the liver during chronic and acute schistosomiasis in mice.
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Acetatos , Ciclopropanos , Modelos Animales de Enfermedad , Ratones Noqueados , Quinolinas , Receptores de Leucotrienos , Esquistosomiasis mansoni , Sulfuros , Animales , Receptores de Leucotrienos/metabolismo , Ratones , Ciclopropanos/uso terapéutico , Ciclopropanos/farmacología , Acetatos/uso terapéutico , Acetatos/farmacología , Sulfuros/uso terapéutico , Sulfuros/farmacología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/inmunología , Esquistosomiasis mansoni/parasitología , Quinolinas/uso terapéutico , Quinolinas/farmacología , Femenino , Schistosoma mansoni/inmunología , Enfermedad Crónica , Antagonistas de Leucotrieno/farmacología , Antagonistas de Leucotrieno/uso terapéutico , Hígado/parasitología , Hígado/patología , Hígado/metabolismo , Hígado/inmunología , Ratones Endogámicos C57BL , Praziquantel/uso terapéutico , Praziquantel/farmacología , Linfocitos T Reguladores/inmunologíaRESUMEN
Montelukast by inhibiting leukotriene receptors in the bladder can prevent the activation of mast cells. We investigated the effectiveness of Montelukast in reducing the symptoms of children with bladder pain syndrome (BPS). In this randomized clinical trial, children were allocated into groups of intervention (Montelukast and oxybutynin) and the control (oxybutynin). At the beginning and after 14 days, questions from mothers of children about their urinary condition were asked about the frequency of nocturnal enuresis, frequent urination, urinary incontinence, urinary urgency, and their pain severity. There was no significant difference between two groups in terms of frequency of nocturnal enuresis, frequent urination, urinary incontinence, and urinary urgency. Regarding the frequency of pain distribution, the frequency of pain-free people in the Montelukast group was higher than control group (84.4% vs 56.3%, P = .023). The results showed that adding Montelukast to oxybutynin has a significant decrease in pain in children with BPS.
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BACKGROUND: Post-marketing surveillance found montelukast use was associated with an increased risk of depression. However, results of observational studies are inconsistent. OBJECTIVE: This study aimed to assess whether montelukast exposure is associated with depression and elucidate the possible molecular mechanism. METHOD: We conducted a cross-sectional study of 9508 adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Multivariable regression was used to evaluate the association between montelukast exposure and depression. Network pharmacology was conducted to identify the mechanisms of montelukast on depression. RESULTS: Montelukast exposure had a higher prevalence of depression (37.4 %). In a multivariable logistic regression model adjusted for sociodemographic, behavioural, and health characteristics, montelukast exposure was associated with depression (odds ratio [OR]: 1.61; confidence interval [CI]: 1.18-2.19). Network pharmacology was identified 69 key targets of montelukast on depression. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested montelukast mainly works through multiple pathways in endocrine resistance, chemical carcinogenesis-receptor activation, estrogen signaling pathway, etc. LIMITATIONS: Cross-sectional data. CONCLUSIONS: The study implies a potential positive association between long-term montelukast exposure and depression through multi-faceted mechanisms. It is suggested that attention be given to the possibility of depression in patients undergoing prolonged montelukast therapy.
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Acetatos , Ciclopropanos , Quinolinas , Sulfuros , Humanos , Acetatos/farmacología , Acetatos/efectos adversos , Quinolinas/farmacología , Quinolinas/efectos adversos , Femenino , Masculino , Estudios Transversales , Adulto , Persona de Mediana Edad , Depresión/tratamiento farmacológico , Encuestas NutricionalesRESUMEN
BACKGROUND: The benefits and harms of adding antileukotrienes to H1 antihistamines (AHs) for the management of urticaria (hives, itch, and/or angioedema) remain unclear. OBJECTIVE: We sought to systematically synthesize the treatment outcomes of antileukotrienes in combination with AHs versus AHs alone for acute and chronic urticaria. METHODS: As part of updating American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma, and Immunology Joint Task Force on Practice Parameters urticaria guidelines, we searched Medline, Embase, Central, LILACS, WPRIM, IBECS, ICTRP, CBM, CNKI, VIP, Wanfang, US Food and Drug Administration, and European Medicines Agency databases from inception to December 18, 2023, for randomized controlled trials (RCTs) evaluating antileukotrienes and AHs versus AHs alone in patients with urticaria. Paired reviewers independently screened citations, extracted data, and assessed risk of bias. Random effects models pooled effect estimates for urticaria activity, itch, wheal, sleep, quality of life, and harms. The GRADE approach informed certainty of evidence ratings. The study was registered at the Open Science Framework (osf.io/h2bfx/). RESULTS: Thirty-four RCTs enrolled 3324 children and adults. Compared to AHs alone, the combination of a leukotriene receptor antagonist with AHs probably modestly reduces urticaria activity (mean difference, -5.04; 95% confidence interval, -6.36 to -3.71; 7-day urticaria activity score) with moderate certainty. We made similar findings for itch and wheal severity as well as quality of life. Adverse events were probably not different between groups (moderate certainty); however, no RCT reported on neuropsychiatric adverse events. CONCLUSION: Among patients with urticaria, adding leukotriene receptor antagonists to AHs probably modestly improves urticaria activity with little to no increase in overall adverse events. The added risk of neuropsychiatric adverse events in this population with leukotriene receptor antagonists is small and uncertain.
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Background and Objectives: The influence of montelukast (MK), an antagonist of cysLT1 leukotriene receptors, on lung lesions caused by experimental diabetes was studied. Materials and Methods: The study was conducted on four groups of six adult male Wistar rats. Diabetes was produced by administration of streptozotocin 65 mg/kg ip. in a single dose. Before the administration of streptozotocin, after 72 h, and after 8 weeks, the serum values of glucose, SOD, MDA, and total antioxidant capacity (TAS) were determined. After 8 weeks, the animals were anesthetized and sacrificed, and the lungs were harvested and examined by optical microscopy. Pulmonary fibrosis, the extent of lung lesions, and the lung wet-weight/dry-weight ratio were evaluated. Results: The obtained results showed that MK significantly reduced pulmonary fibrosis (3.34 ± 0.41 in the STZ group vs. 1.73 ± 0.24 in the STZ+MK group p < 0.01) and lung lesion scores and also decreased the lung wet-weight/dry-weight (W/D) ratio. SOD and TAS values increased significantly when MK was administered to animals with diabetes (77.2 ± 11 U/mL in the STZ group vs. 95.7 ± 13.3 U/mL in the STZ+MK group, p < 0.05, and 25.52 ± 2.09 Trolox units in the STZ group vs. 33.29 ± 1.64 Trolox units in the STZ+MK group, respectively, p < 0.01), and MDA values decreased. MK administered alone did not significantly alter any of these parameters in normal animals. Conclusions: The obtained data showed that by blocking the action of peptide leukotrienes on cysLT1 receptors, montelukast significantly reduced the lung lesions caused by diabetes. The involvement of these leukotrienes in the pathogenesis of fibrosis and other lung diabetic lesions was also demonstrated.
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Acetatos , Ciclopropanos , Diabetes Mellitus Experimental , Pulmón , Quinolinas , Ratas Wistar , Sulfuros , Ciclopropanos/uso terapéutico , Animales , Quinolinas/uso terapéutico , Quinolinas/farmacología , Acetatos/uso terapéutico , Acetatos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/fisiopatología , Masculino , Ratas , Pulmón/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Antagonistas de Leucotrieno/uso terapéutico , Antagonistas de Leucotrieno/farmacología , Estreptozocina , Glucemia/análisis , Glucemia/efectos de los fármacosRESUMEN
A green, sensitive and rapid spectrofluorimetric method for quantitative assay of an anti-allergic medication composed of montelukast and fexofenadine mixture in raw materials and dosage form was developed. The method was based on measuring the synchronous fluorimetric peak without interference, pre-separation or pre-extraction procedures. Montelukast was analyzed at 360 nm while fexofenadine was measured at 263 nm using Δλ = 20 nm for both drugs using ethanol as diluting solvent and acetate buffer of pH 4. The assay was rectilinear over the concentration range of 1.0-10.0 µg/mL for fexofenadine and 0.1-0.6 µg/mL for montelukast. The method was full validated according to ICH guidelines. The applicability of the method enables the assay of both drugs in raw materials, synthetic mixture as well as combined tablets. Moreover, the greenness of the method was assessed using different methods including; analytical eco-scale, GAPI and AGREE. All of these methods confirm that the proposed method is an eco-friendly method.
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Acetatos , Antialérgicos , Ciclopropanos , Quinolinas , Espectrometría de Fluorescencia , Sulfuros , Terfenadina , Espectrometría de Fluorescencia/métodos , Terfenadina/análisis , Terfenadina/análogos & derivados , Quinolinas/análisis , Quinolinas/química , Acetatos/análisis , Sulfuros/análisis , Sulfuros/química , Antialérgicos/análisis , Tecnología Química Verde/métodos , Comprimidos , Reproducibilidad de los Resultados , Límite de Detección , Formas de Dosificación , Concentración de Iones de HidrógenoRESUMEN
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.
Asunto(s)
Acetatos , Tonsila Faríngea , Ciclopropanos , Hipertrofia , Antagonistas de Leucotrieno , Furoato de Mometasona , Quinolinas , Sulfuros , Humanos , Tonsila Faríngea/patología , Ciclopropanos/uso terapéutico , Quinolinas/uso terapéutico , Acetatos/uso terapéutico , Acetatos/administración & dosificación , Hipertrofia/tratamiento farmacológico , Niño , Furoato de Mometasona/uso terapéutico , Furoato de Mometasona/administración & dosificación , Antagonistas de Leucotrieno/uso terapéutico , Antagonistas de Leucotrieno/administración & dosificación , Administración Intranasal , Quimioterapia Combinada , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron (MN) loss and consequent muscle atrophy, for which no effective therapies are available. Recent findings reveal that disease progression is fuelled by early aberrant neuroinflammation and the loss of oligodendrocytes with neuroprotective and remyelinating properties. On this basis, pharmacological interventions capable of restoring a pro-regenerative local milieu and re-establish proper oligodendrocyte functions may be beneficial. EXPERIMENTAL APPROACH: Here, we evaluated the in vivo therapeutic effects of montelukast (MTK), an antagonist of the oligodendroglial G protein-coupled receptor 17 (GPR17) and of cysteinyl-leukotriene receptor 1 (CysLT1R) receptors on microglia and astrocytes, in the SOD1G93A ALS mouse model. We chronically treated SOD1G93A mice with MTK, starting from the early symptomatic disease stage. Disease progression was assessed by behavioural and immunohistochemical approaches. KEY RESULTS: Oral MTK treatment significantly extended survival probability, delayed body weight loss and ameliorated motor functionalityonly in female SOD1G93A mice. Noteworthy, MTK significantly restored oligodendrocyte maturation and induced significant changes in the reactive phenotype and morphological features of microglia/macrophages and astrocytes in the spinal cord of female SOD1G93A mice, suggesting enhanced pro-regenerative functions. Importantly, concomitant MN preservation has been detected after MTK administration. No beneficial effects were observed in male mice, highlighting a sex-based difference in the protective activity of MTK. CONCLUSIONS AND IMPLICATIONS: Our results provide the first preclinical evidence indicating that repurposing of MTK, a safe and marketed anti-asthmatic drug, may be a promising sex-specific strategy for personalized ALS treatment.
Asunto(s)
Acetatos , Esclerosis Amiotrófica Lateral , Ciclopropanos , Ratones Transgénicos , Oligodendroglía , Quinolinas , Sulfuros , Animales , Femenino , Ciclopropanos/farmacología , Quinolinas/farmacología , Acetatos/farmacología , Acetatos/uso terapéutico , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , Oligodendroglía/patología , Sulfuros/farmacología , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/patología , Ratones , Masculino , Receptores de Leucotrienos/metabolismo , Receptores de Leucotrienos/genética , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Proteínas del Tejido NerviosoRESUMEN
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.