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Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation

Madrid et al., Heliyon, doi:10.1016/j.heliyon.2020.e05820
Dec 2020  
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Ivermectin for COVID-19
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*, now known with p < 0.00000000001 from 102 studies, recognized in 22 countries.
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In vivo analysis of the safety of high dose ivermectin with a Corydoras fish animal model.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Jitobaom, Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Jitobaom, 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 inhibits importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), inhibits SARS-CoV-2 3CLpro Mody, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing Fauquet, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, Scheim, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 via IMPase inhibition Jitobaom, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, may inhibit SARS-CoV-2 RdRp activity Parvez (B), may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation Liu (C), shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing 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 Bifidobacteria which play 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.
Madrid et al., 31 Dec 2020, peer-reviewed, 8 authors.
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Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation
Rafael R M Madrid, Patrick D Mathews, Ana C M F Patta, Anai P Gonzales-Flores, Carlos A B Ramirez, Vera L S Rigoni, Marcos Tavares-Dias, Omar Mertins
Heliyon, doi:10.1016/j.heliyon.2020.e05820
The FDA-approved drug ivermectin is applied for treatments of onchocerciasis and lymphatic filariasis. The anticancer and anti-viral activities have been demonstrated stressing possibilities for the drug repurposing and therefore new information on high dosage safety is on demand. We analyzed in vivo tissue responses for high doses of ivermectin using Corydoras fish as animal model. We made intestinal histology and hematologic assays after oral administration of ivermectin transported with polyelectrolytes formulation. Histology showed any apparent damage of intestinal tissues at 0.22-170 mg of ivermectin/kg body weight. Immunofluorescence evidenced delocalization of Myosin-Vb at enterocytes only for the higher dose. Hematology parameters showed random variations after 7 days from administration, but a later apparent recover after 14 and 21 days. The study evaluated the potential of high doses of oral administration of ivermectin formulation, which could be an alternative with benefits in high compliance therapies.
Declaration of interests statement The authors declare no conflict of interest. Additional information Supplementary content related to this article has been published online at
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