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Pharmacokinetics and Safety of Inhaled Ivermectin in Mice as a Potential COVID-19 Treatment

Albariqi et al., International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2022.121688
Mar 2022  
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Mouse study of an inhaled ivermectin formulation, showing high concentrations in the lung and bronchoalveolar lavage fluid, exceeding the required concentration for efficacy based on in vitro studies.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin is an inhibitor of importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), a SARS-CoV-2 3CLpro inhibitor Mody, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model of severe infection/inflammation that shares key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacterium which plays a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
6 studies investigate novel formulations of ivermectin for improved efficacy Albariqi, Albariqi (B), Chaccour, Errecalde, Mansour, Saha (B)
Albariqi et al., 18 Mar 2022, peer-reviewed, 9 authors.
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Pharmacokinetics and safety of inhaled ivermectin in mice as a potential COVID-19 treatment
Ahmed H Albariqi, Yuncheng Wang, Rachel Yoon Kyung Chang, Diana H Quan, Xiaonan Wang, Stefanie Kalfas, John Drago, Warwick J Britton, Hak-Kim Chan
International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2022.121688
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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