Montelukast Drug May Improve COVID-19 Prognosis: A Review of Evidence

Barre, Jean La; Sabatier, Jean‐Marc; Annweiler, Cédric

doi:10.3389/fphar.2020.01344

Cited by 38 publications

(46 citation statements)

References 55 publications

(59 reference statements)

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“…As outlined in the introduction, there is a current interest in repurposing of MTK for the treatment of patients with neurodegenerative diseases such as dementia patients 17,20,21 , and of COVID-19 patients 22,23 . Both show dysphagia, and therefore, a mucoadhesive film might have certain advantages.…”

Section: Resultsmentioning

confidence: 99%

Improved bioavailability of montelukast through a novel oral mucoadhesive film in humans and mice

Michael

Sousa

Conway³

et al. 2020

Preprint

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The leukotriene receptor antagonist Montelukast (MTK) is an approved medication for the treatment of asthma and allergic rhinitis. The existing marketed tablet forms of MTK exhibit inconsistent uptake and bioavailability, which partially explains the presence of a significant proportion of MTK low and non-responders in the population. Besides that, tablets are suboptimal formulations for patients suffering of dysphagia, for example seen in COVID19 patients or in patients with neurodegenerative diseases such as Alzheimers Disease. The increasing interest in repurposing of MTK for the treatment of such patients and the need for an improved bioavailability triggered us to reformulate MTK. The aim was to develop a mucoadhesive MTK film with a good safety and improved pharmacological, i.e. improved bioavailability, profile in humans as well as in a mouse model of Alzheimers Disease. We tested dissolution of the mucoadhesive film containing MTK in saliva buffer and assessed pharmacoexposure and kinetics after acute and chronic oral application in mice. Furthermore, we performed a Phase I safety / bioavailability / pharmacokinetic analysis in healthy volunteers. The latter included a comparison with the marketed tablet form as well as a quantitative analysis of the MTK levels in the cerebrospinal fluid. The novel MTK film demonstrated significantly improved bioavailability compared to the marketed tablet in the clinical phase 1a study in healthy humans. Furthermore, there were measurable amounts of MTK present in the cerebrospinal fluid (CSF) at the 3.0 and 7.0 hour time points post drug administration in humans. In mice, MTK was detected in serum and CSF after acute and chronic exposure in a dose dependent manner. The developed mucoadhesive film of MTK represents a promising alternative for the tablet delivery. The oral film might lower the non-responder rate in patients with asthma and might be an interesting product for repurposing of MTK in other diseases. As we demonstrate BBB penetrance in a preclinical model as well as in a clinical study, the oral film of MTK might find its use as a therapeutic for acute and chronic neurodegenerative diseases such as dementias and stroke.

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Section: Resultsmentioning

confidence: 99%

Improved bioavailability of montelukast through a novel oral mucoadhesive film in humans and mice

Michael

Sousa

Conway³

et al. 2020

Preprint

View full text Add to dashboard Cite

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“… Barré et al, 2020 ; Şener et al, 2006 ; Zhang et al, 2020b .…”

Section: Uncited Referencesunclassified

Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity

Al-Kuraishy

Al-Gareeb

Almulaiky

et al. 2021

European Journal of Pharmacology

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Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the responsible agent for the coronavirus disease 2019 (Covid-19), has its entry point through interaction with angiotensin converting enzyme 2 (ACE2) receptors, highly expressed in lung type II alveolar cells and other tissues, like heart, pancreas, brain, and vascular endothelium. This review aimed to elucidate the potential role of leukotrienes (LTs) in the pathogenesis and clinical presentation of SARS-CoV-2 infection, and to reveal the critical role of LT pathway receptor antagonists and inhibitors in Covid-19 management. A literature search was done in PubMed, Scopus, Web of Science and Google Scholar databases to find the potential role of montelukast and other LT inhibitors in the management of pulmonary and extra-pulmonary manifestations triggered by SARS-CoV-2. Data obtained so far underline that pulmonary and extra-pulmonary manifestations in Covid-19 are attributed to a direct effect of SARS-CoV-2 in expressed ACE2 receptors or indirectly through NF-κB dependent induction of a cytokine storm. Montelukast can ameliorate extra-pulmonary manifestations in Covid-19 either directly through blocking of Cys-LTRs in different organs or indirectly through inhibition of the NF-κB signaling pathway.

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“…Plus, it has been demonstrated that Montelukast can reduce neuroinflammation and induce neurogenesis by GPR17 receptor. Several studies showed that Montelukast can mitigate cytokine storms and reduce interaction between SARS-CoV-2 and ACE2, as well as increase mitochondrial mass and function at systemic level [ 278 ].…”

Section: Antioxidants As Neuroprotectors In Patients Infected With Covid-19mentioning

confidence: 99%

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

et al. 2021

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Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is an emergent infectious disease that has caused millions of deaths throughout the world. COVID-19 infection’s main symptoms are fever, cough, fatigue, and neurological manifestations such as headache, myalgias, anosmia, ageusia, impaired consciousness, seizures, and even neuromuscular junctions’ disorders. In addition, it is known that this disease causes a series of systemic complications such as adverse respiratory distress syndrome, cardiac injury, acute kidney injury, and liver dysfunction. Due to the neurological symptoms associated with COVID-19, damage in the central nervous system has been suggested as well as the neuroinvasive potential of SARS-CoV-2. It is known that CoV infections are associated with an inflammation process related to the imbalance of the antioxidant system; cellular changes caused by oxidative stress contribute to brain tissue damage. Although anti-COVID-19 vaccines are under development, there is no specific treatment for COVID-19 and its clinical manifestations and complications; only supportive treatments with immunomodulators, anti-vascular endothelial growth factors, modulating drugs, statins, or nutritional supplements have been used. In the present work, we analyzed the potential of antioxidants as adjuvants for the treatment of COVID-19 and specifically their possible role in preventing or decreasing the neurological manifestations and neurological complications present in the disease.

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Montelukast Drug May Improve COVID-19 Prognosis: A Review of Evidence

Cited by 38 publications

References 55 publications

Improved bioavailability of montelukast through a novel oral mucoadhesive film in humans and mice

Improved bioavailability of montelukast through a novel oral mucoadhesive film in humans and mice

Role of leukotriene pathway and montelukast in pulmonary and extrapulmonary manifestations of Covid-19: The enigmatic entity

Use of Antioxidants for the Neuro-Therapeutic Management of COVID-19

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