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All Studies   Meta Analysis    Recent:   

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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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,800+ studies for 95 treatments. c19ivm.org
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.
68 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.
7 studies investigate novel formulations of ivermectin for improved efficacy38,58,59,64,86-88
Albariqi et al., 18 Mar 2022, peer-reviewed, 9 authors.
This PaperIvermectinAll
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.
References
Albariqi, Conceptualization, Methodology, Investigation, Formal analysis, Data curation, Visualization
Albariqi, Ke, Khanal, Kalfas, Tang et al., Preparation and Characterisation of inhalable ivermectin powders as a potential COVID-19 therapy, J. Aerosol Med. Pulm. Drug Deliv
Callaway, Omicron likely to weaken COVID vaccine protection, Nature
Caly, Druce, Catton, Jans, Wagstaff, The FDAapproved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res
Chaccour, Abizanda, Irigoyen-Barrio, Casellas, Aldaz et al., Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats, Sci. Rep
Chaccour, Hammann, Rabinovich, Ivermectin to reduce malaria transmission I. Pharmacokinetic and pharmacodynamic considerations regarding efficacy and safety, Malar. J
Competing Interest, Hkc, AHA are inventors of a provisional patent
Cornberg, Buti, Eberhardt, Grossi, Shouval, EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients, J. Hepatol
Errecalde, Lifschitz, Vecchioli, Ceballos, Errecalde et al., Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model, J. Pharm. Sci
Gatti, De Ponti, Drug Repurposing in the COVID-19 Era: Insights from Case Studies Showing Pharmaceutical Peculiarities, Pharmaceutics
Gilbert, Slechta, A Case of Ivermectin-Induced Warfarin Toxicity: First Published Report, Hosp. Pharm
Guzzo, Furtek, Porras, Chen, Tipping et al., Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects, J. Clin. Pharmacol
Hadj Hassine, Covid-19 vaccines and variants of concern: A review, Rev. Med. Virol
Kumar, Ter Ellen, Bouma, Troost, Van De Pol et al., Moxidectin and Ivermectin Inhibit Sars-Cov-2 Replication in Vero E6 Cells but Not in Human Primary Airway Epithelium Cells, Antimicrob. Agents Chemother
Lespine, Alvinerie, Sutra, Pors, Chartier, Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat, Vet. Parasitol
Lifschitz, Virkel, Sallovitz, Sutra, Galtier et al., Comparative distribution of ivermectin and doramectin to parasite location tissues in cattle, Vet. Parasitol
Lundberg, Pinkham, Baer, Amaya, Narayanan et al., Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication, Antiviral Res
Lv, Liu, Wang, Dang, Qiu et al., Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo, Antiviral Res
Mansour, Shamma, Ahmed, Sabry, Esmat et al., Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study, Int. Immunopharmacol
Mastrangelo, Pezzullo, De Burghgraeve, Kaptein, Pastorino et al., Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug, J. Antimicrob. Chemother
Nicolas, Maia, Bassat, Kobylinski, Monteiro et al., Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis, Lancet Glob Health
Omura, Crump, Ivermectin: panacea for resource-poor communities?, Trends Parasitol
Omura, Ivermectin: 25 years and still going strong, Int J Antimicrob Agents
Phillips, Inhaled efficacious dose translation from rodent to human: A retrospective analysis of clinical standards for respiratory diseases, Pharmacol. Ther
Pilcer, Amighi, Formulation strategy and use of excipients in pulmonary drug delivery, Int. J. Pharm
Qiu, Liao, Chow, Lam, Intratracheal Administration of Dry Powder Formulation in Mice, J Vis Exp
Quan, Conceptualization, Validation, Data curation
Sallam, COVID-19 Vaccine Hesitancy Worldwide: A Concise Systematic Review of Vaccine Acceptance Rates, Vaccines
Walters, Lung lining liquid -the hidden depths. The 5th Nils W. Svenningsen memorial lecture, Biol. Neonate
Wang, Methodology, Investigation. Stefanie Kalfas: Formal analysis, Data curation, Writing-review & editing John Drago: Formal analysis, Data curation, Writing -review & editing Warwick J Britton: Conceptualization, Resources, Supervision, Writing-review & editing
Wang, Validation, Methodology, Investigation, Formal analysis, Data curation
Wouters, Shadlen, Salcher-Konrad, Pollard, Larson et al., Challenges in ensuring global access to COVID-19 vaccines: production, affordability, allocation, and deployment, Lancet
Yoon, Chang, Conceptualization, Validation, Data curation
Zhang, Huo, Zhou, Xie, PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel, Comput. Methods Programs Biomed
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