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All Studies   Meta Analysis    Recent:   

Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study

Mansour et al., International Immunopharmacology, doi:10.1016/j.intimp.2021.108004
Jul 2021  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 104 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19ivm.org
Safety analysis of an inhaled lyophilized ivermectin formulation, showing 127-fold increase in drug solubility, and identifying safe dosage levels in rats.
7 studies investigate novel formulations of ivermectin for improved efficacy1-7
Mansour et al., 23 Jul 2021, peer-reviewed, 7 authors.
This PaperIvermectinAll
Safety of inhaled ivermectin as a repurposed direct drug for treatment of COVID-19: A preclinical tolerance study
Suzan M. Mansour, Rehab N. Shamma, Kawkab A. Ahmed, Nirmeen A. Sabry, Gamal Esmat, Azza A. Mahmoud, Amr Maged
International Immunopharmacology, doi:10.1016/j.intimp.2021.108004
Introduction: SARS-CoV-2 replication in cell cultures has been shown to be inhibited by ivermectin. However, ivermectin's low aqueous solubility and bioavailability hinders its application in COVID-19 treatment. Also, it has been suggested that best outcomes for this medication can be achieved via direct administration to the lung. Objectives: This study aimed at evaluating the safety of a novel ivermectin inhalable formulation in rats as a preclinical step. Methods: Hydroxy propyl-β-cyclodextrin (HP-β-CD) was used to formulate readily soluble ivermectin lyophilized powder. Adult male rats were used to test lung toxicity for ivermectin-HP-β-CD formulations in doses of 0.05, 0.1, 0.2, 0.4 and 0.8 mg/kg for 3 successive days. Results: The X-ray diffraction for lyophilized ivermectin-HP-β-CD revealed its amorphous structure that increased drug aqueous solubility 127-fold and was rapidly dissolved within 5 s in saline. Pulmonary administration of ivermectin-HP-β-CD in doses of 0.2, 0.4 and 0.8 mg/kg showed dose-dependent increase in levels of TNF-α, IL-6, IL-13 and ICAM-1 as well as gene expression of MCP-1, protein expression of PIII-NP and serum levels of SP-D paralleled by reduction in IL-10. Moreover, lungs treated with ivermectin (0.2 mg/kg) revealed mild histopathological alterations, while severe pulmonary damage was seen in rats treated with ivermectin at doses of 0.4 and 0.8 mg/kg. However, ivermectin-HP-β-CD formulation administered in doses of 0.05 and 0.1 mg/kg revealed safety profiles. Conclusion: The safety of inhaled ivermectin-HP-β-CD formulation is dose-dependent. Nevertheless, use of low doses (0.05 and 0.1 mg/kg) could be considered as a possible therapeutic regimen in COVID-19 cases.
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