Variations in Plasma Levels of Orally Administered Ivermectin Could Hamper Its Potential Drug Repositioning: Results of a Bioequivalence Study in Mexican Population

DOI record: { "DOI": "10.3390/ph18081193", "ISSN": [ "1424-8247" ], "URL": "http://dx.doi.org/10.3390/ph18081193", "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>", "alternative-id": [ "ph18081193" ], "author": [ { "affiliation": [ { "name": "Chemical Sciences School, Universidad La Salle-México, Benjamín Franklin 45, Mexico City 06140, Mexico" } ], "family": "de la Puente", "given": "Ernesto", "sequence": "first" }, { "affiliation": [ { "name": "Chemical Sciences School, Universidad La Salle-México, Benjamín Franklin 45, Mexico City 06140, Mexico" } ], "family": "Ramos-Mundo", "given": "Carlos", "sequence": "additional" }, { "affiliation": [ { "name": "Chemical Sciences School, Universidad La Salle-México, Benjamín Franklin 45, Mexico City 06140, Mexico" } ], "family": "Flores-Pérez", "given": "Elena I.", "sequence": "additional" }, { "affiliation": [ { "name": "Research Group on Development and Innovation in Health and Nutrition Promotion and Education, Universidad La Salle-México, Benjamín Franklin 45, Mexico City 06140, Mexico" } ], "family": "Vergara-Castañeda", "given": "Arely", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-6498-3286", "affiliation": [ { "name": "Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Mexico City 14610, Mexico" } ], "authenticated-orcid": false, "family": "Reyes-Grajeda", "given": "Juan Pablo", "sequence": "additional" }, { "affiliation": [ { "name": "Facultad de Química, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico" } ], "family": "Medina-Reyes", "given": "Liz J.", "sequence": "additional" }, { "affiliation": [ { "name": "Chemical Sciences School, Universidad La Salle-México, Benjamín Franklin 45, Mexico City 06140, Mexico" } ], "family": "Ruiz-Olmedo", "given": "María Isabel", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-8449-0806", "affiliation": [ { "name": "Design, Isolation, and Synthesis of Bioactive Molecules Research Group, Universidad La Salle-México, Benjamín Franklin 45, Mexico City 06140, Mexico" } ], "authenticated-orcid": false, "family": "Loza-Mejía", "given": "Marco A.", "sequence": "additional" } ], "container-title": "Pharmaceuticals", "container-title-short": "Pharmaceuticals", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 8, 13 ] ], "date-time": "2025-08-13T09:43:01Z", "timestamp": 1755078181000 }, "deposited": { "date-parts": [ [ 2025, 8, 13 ] ], "date-time": "2025-08-13T09:48:50Z", "timestamp": 1755078530000 }, "indexed": { "date-parts": [ [ 2025, 8, 15 ] ], "date-time": "2025-08-15T02:35:59Z", "timestamp": 1755225359640, "version": "3.43.0" }, "is-referenced-by-count": 0, "issue": "8", "issued": { "date-parts": [ [ 2025, 8, 13 ] ] }, "journal-issue": { "issue": "8", "published-online": { "date-parts": [ [ 2025, 8 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 8, 13 ] ], "date-time": "2025-08-13T00:00:00Z", "timestamp": 1755043200000 } } ], "link": [ { "URL": "https://www.mdpi.com/1424-8247/18/8/1193/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "1193", "prefix": "10.3390", "published": { "date-parts": [ [ 2025, 8, 13 ] ] }, "published-online": { "date-parts": [ [ 2025, 8, 13 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.1007/978-1-4939-8955-3", "doi-asserted-by": "crossref", "key": "ref_1", "unstructured": "Vanhaelen, Q. 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