Variations in Plasma Levels of Orally Administered Ivermectin Could Hamper Its Potential Drug Repositioning: Results of a Bioequivalence Study in Mexican Population
et al., Pharmaceuticals, doi:10.3390/ph18081193, Aug 2025
Ivermectin for COVID-19
4th treatment shown to reduce risk in
August 2020, now with p < 0.00000000001 from 106 studies, recognized in 24 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
Bioequivalence study of 66 healthy Mexican volunteers comparing two oral ivermectin formulations, showing significant pharmacokinetic variability. The study found high inter- and intra-subject variability (>50% coefficient of variation) in maximum plasma concentration (Cmax) and area under the curve (AUC), with the test formulation producing slightly higher but highly variable drug exposure compared to the reference formulation. However analysis was done with fasting, and results may be different with the standard protocol for COVID-19 where administration is done with a high-fat meal, which significantly increases plasma concentration1.
74 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 H7N772, Dengue38,73,74 , HIV-174, Simian virus 4075, Zika38,76,77 , West Nile77, Yellow Fever78,79, Japanese encephalitis78, Chikungunya79, Semliki Forest virus79, Human papillomavirus58, Epstein-Barr58, BK Polyomavirus80, and Sindbis virus79.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins72,74,75,81 , shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing39, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination42,82, shows dose-dependent inhibition of wildtype and omicron variants37, exhibits dose-dependent inhibition of lung injury62,67, may inhibit SARS-CoV-2 via IMPase inhibition38, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation10, inhibits SARS-CoV-2 3CLpro55, may inhibit SARS-CoV-2 RdRp activity29, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages61, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation83, may interfere with SARS-CoV-2's immune evasion via ORF8 binding5, may inhibit SARS-CoV-2 by disrupting CD147 interaction84-87, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1960,88, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage9, may minimize SARS-CoV-2 induced cardiac damage41,49, may counter immune evasion by inhibiting NSP15-TBK1/KPNA1 interaction and restoring IRF3 activation89, may disrupt SARS-CoV-2 N and ORF6 protein nuclear transport and their suppression of host interferon responses2, reduces TAZ/YAP nuclear import, relieving SARS-CoV-2-driven suppression of IRF3 and NF-κB antiviral pathways36, increases Bifidobacteria which play a key role in the immune system90, has immunomodulatory52 and anti-inflammatory71,91 properties, and has an extensive and very positive safety profile92.
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de la Puente et al., 13 Aug 2025, Mexico, peer-reviewed, 8 authors.
Contact: marcoantonio.loza@lasalle.mx (corresponding author), juande@lasallistas.org.mx, ei.flores@lasallistas.org.mx, mruiz@lasallistas.org.mx, arely.vergara@lasalle.mx, jreyes@inmegen.gob.mx, lizmedina@quimica.unam.mx.
Variations in Plasma Levels of Orally Administered Ivermectin Could Hamper Its Potential Drug Repositioning: Results of a Bioequivalence Study in Mexican Population
Pharmaceuticals, doi:10.3390/ph18081193
Background/Objectives: Despite its initial promise as a treatment for COVID-19 due to its antiviral properties, controlled randomized trials have demonstrated a lack of clinical efficacy at standard dosages. Although its overall clinical benefits remain contentious, a recent meta-analysis suggests that ivermectin may lower the risk of mechanical ventilation in COVID-19 patients. This study aims to assess the bioequivalence of different formulations of orally administered ivermectin within a Mexican population. Methods: A randomized, controlled bioequivalence study was conducted involving healthy volunteers who received two oral formulations of ivermectin. Plasma samples were collected at predetermined intervals for pharmacokinetic analysis. Results: The findings indicate significant variations in plasma concentration profiles among the evaluated formulations. Elevated inter-and intrasubject variations, independent of the formulation, highlighted implications for both clinical efficacy and safety. Conclusions: The potential repurposing of ivermectin for COVID-19 treatment raises concerns, particularly regarding the variability in plasma levels resulting from oral administration, which may impact its effectiveness. The study underscores the importance of pharmacokinetic properties in the repurposing of ivermectin as a therapeutic agent. Given the observed discrepancies in plasma levels, careful consideration of dosing and formulation is essential for optimizing clinical outcomes in potential new applications of ivermectin.
Conflicts of Interest: The authors declare no conflicts of interest.
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"abstract": "<jats:p>Background/Objectives: Despite its initial promise as a treatment for COVID-19 due to its antiviral properties, controlled randomized trials have demonstrated a lack of clinical efficacy at standard dosages. Although its overall clinical benefits remain contentious, a recent meta-analysis suggests that ivermectin may lower the risk of mechanical ventilation in COVID-19 patients. This study aims to assess the bioequivalence of different formulations of orally administered ivermectin within a Mexican population. Methods: A randomized, controlled bioequivalence study was conducted involving healthy volunteers who received two oral formulations of ivermectin. Plasma samples were collected at predetermined intervals for pharmacokinetic analysis. Results: The findings indicate significant variations in plasma concentration profiles among the evaluated formulations. Elevated inter- and intrasubject variations, independent of the formulation, highlighted implications for both clinical efficacy and safety. Conclusions: The potential repurposing of ivermectin for COVID-19 treatment raises concerns, particularly regarding the variability in plasma levels resulting from oral administration, which may impact its effectiveness. The study underscores the importance of pharmacokinetic properties in the repurposing of ivermectin as a therapeutic agent. Given the observed discrepancies in plasma levels, careful consideration of dosing and formulation is essential for optimizing clinical outcomes in potential new applications of ivermectin.</jats:p>",
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