Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model

Autores
Errecalde, Jorge Oscar; Lifschitz, Adrian Luis; Vecchioli, Graciela Isabel; Ceballos, Laura; Errecalde, Francisco; Ballent, Mariana; Marín, Gustavo Horacio; Daniele, Martín Rafael; Turic, Esteban; Spitzer, Eduardo; Toneguzzo, Fernando; Gold, Silvia; Krolewiecki, Alejandro J.; Alvarez, Luis; Lanusse, Carlos Edmundo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Recently published data indicates that high ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.
Facultad de Ciencias Médicas
Facultad de Ciencias Veterinarias
Materia
Medicina
Biología
Ivermectin
Covid 19
Nasal-spray formulation
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-nd/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/134952

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network_name_str SEDICI (UNLP)
spelling Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig ModelErrecalde, Jorge OscarLifschitz, Adrian LuisVecchioli, Graciela IsabelCeballos, LauraErrecalde, FranciscoBallent, MarianaMarín, Gustavo HoracioDaniele, Martín RafaelTuric, EstebanSpitzer, EduardoToneguzzo, FernandoGold, SilviaKrolewiecki, Alejandro J.Alvarez, LuisLanusse, Carlos EdmundoMedicinaBiologíaIvermectinCovid 19Nasal-spray formulationRecently published data indicates that high ivermectin (IVM) concentrations suppress <i>in vitro</i> SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.Facultad de Ciencias MédicasFacultad de Ciencias Veterinarias2021-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf2501-2507http://sedici.unlp.edu.ar/handle/10915/134952enginfo:eu-repo/semantics/altIdentifier/issn/1520-6017info:eu-repo/semantics/altIdentifier/issn/0022-3549info:eu-repo/semantics/altIdentifier/doi/10.1016/j.xphs.2021.01.017info:eu-repo/semantics/altIdentifier/pmid/33493479info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/4.0/Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-10-22T17:13:21Zoai:sedici.unlp.edu.ar:10915/134952Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-10-22 17:13:21.382SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
title Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
spellingShingle Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
Errecalde, Jorge Oscar
Medicina
Biología
Ivermectin
Covid 19
Nasal-spray formulation
title_short Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
title_full Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
title_fullStr Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
title_full_unstemmed Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
title_sort Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model
dc.creator.none.fl_str_mv Errecalde, Jorge Oscar
Lifschitz, Adrian Luis
Vecchioli, Graciela Isabel
Ceballos, Laura
Errecalde, Francisco
Ballent, Mariana
Marín, Gustavo Horacio
Daniele, Martín Rafael
Turic, Esteban
Spitzer, Eduardo
Toneguzzo, Fernando
Gold, Silvia
Krolewiecki, Alejandro J.
Alvarez, Luis
Lanusse, Carlos Edmundo
author Errecalde, Jorge Oscar
author_facet Errecalde, Jorge Oscar
Lifschitz, Adrian Luis
Vecchioli, Graciela Isabel
Ceballos, Laura
Errecalde, Francisco
Ballent, Mariana
Marín, Gustavo Horacio
Daniele, Martín Rafael
Turic, Esteban
Spitzer, Eduardo
Toneguzzo, Fernando
Gold, Silvia
Krolewiecki, Alejandro J.
Alvarez, Luis
Lanusse, Carlos Edmundo
author_role author
author2 Lifschitz, Adrian Luis
Vecchioli, Graciela Isabel
Ceballos, Laura
Errecalde, Francisco
Ballent, Mariana
Marín, Gustavo Horacio
Daniele, Martín Rafael
Turic, Esteban
Spitzer, Eduardo
Toneguzzo, Fernando
Gold, Silvia
Krolewiecki, Alejandro J.
Alvarez, Luis
Lanusse, Carlos Edmundo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Medicina
Biología
Ivermectin
Covid 19
Nasal-spray formulation
topic Medicina
Biología
Ivermectin
Covid 19
Nasal-spray formulation
dc.description.none.fl_txt_mv Recently published data indicates that high ivermectin (IVM) concentrations suppress <i>in vitro</i> SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.
Facultad de Ciencias Médicas
Facultad de Ciencias Veterinarias
description Recently published data indicates that high ivermectin (IVM) concentrations suppress <i>in vitro</i> SARS-CoV-2 replication. Nasal IVM spray administration may contribute to attaining high drug concentrations in nasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM either orally (0.2 mg/kg) or by one or two nasal spray doses. The overall safety, and histopathology of the IVM-spray application site tissues, were assessed. The IVM concentration profiles measured in plasma and respiratory tract tissues after the nasal spray were compared with those achieved after the oral administration. Animals tolerated well the nasal spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in nasopharyngeal and lung tissues. The nasal/oral IVM concentration ratios in nasopharyngeal and lung tissues markedly increased by repeating (12 h apart) the spray application. The fast attainment of high and persistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oral route. These original results support the undertaking of future clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the prevention and/or treatment of COVID-19.
publishDate 2021
dc.date.none.fl_str_mv 2021-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/134952
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dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1520-6017
info:eu-repo/semantics/altIdentifier/issn/0022-3549
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.xphs.2021.01.017
info:eu-repo/semantics/altIdentifier/pmid/33493479
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
dc.format.none.fl_str_mv application/pdf
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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