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Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection

Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its ch...

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Autores principales: Castro-Balado, Ana, Mondelo-García, Cristina, Barbosa-Pereira, Letricia, Varela-Rey, Iria, Novo-Veleiro, Ignacio, Vázquez-Agra, Néstor, Antúnez-López, José Ramón, Bandín-Vilar, Enrique José, Sendón-García, Raquel, Busto-Iglesias, Manuel, Rodríguez-Bernaldo de Quirós, Ana, García-Quintanilla, Laura, González-Barcia, Miguel, Zarra-Ferro, Irene, Otero-Espinar, Francisco J., Rey-Bretal, David, Lago-Quinteiro, José Ramón, Valdés-Cuadrado, Luis, Rábade-Castedo, Carlos, del Río-Garma, María Carmen, Crespo-Diz, Carlos, Delgado-Sánchez, Olga, Aguiar, Pablo, Barbeito-Castiñeiras, Gema, Pérez del Molino-Bernal, María Luisa, Trastoy-Pena, Rocío, Passannante, Rossana, Llop, Jordi, Pose-Reino, Antonio, Fernández-Ferreiro, Anxo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999202/
https://www.ncbi.nlm.nih.gov/pubmed/33808025
http://dx.doi.org/10.3390/pharmaceutics13030342
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author Castro-Balado, Ana
Mondelo-García, Cristina
Barbosa-Pereira, Letricia
Varela-Rey, Iria
Novo-Veleiro, Ignacio
Vázquez-Agra, Néstor
Antúnez-López, José Ramón
Bandín-Vilar, Enrique José
Sendón-García, Raquel
Busto-Iglesias, Manuel
Rodríguez-Bernaldo de Quirós, Ana
García-Quintanilla, Laura
González-Barcia, Miguel
Zarra-Ferro, Irene
Otero-Espinar, Francisco J.
Rey-Bretal, David
Lago-Quinteiro, José Ramón
Valdés-Cuadrado, Luis
Rábade-Castedo, Carlos
del Río-Garma, María Carmen
Crespo-Diz, Carlos
Delgado-Sánchez, Olga
Aguiar, Pablo
Barbeito-Castiñeiras, Gema
Pérez del Molino-Bernal, María Luisa
Trastoy-Pena, Rocío
Passannante, Rossana
Llop, Jordi
Pose-Reino, Antonio
Fernández-Ferreiro, Anxo
author_facet Castro-Balado, Ana
Mondelo-García, Cristina
Barbosa-Pereira, Letricia
Varela-Rey, Iria
Novo-Veleiro, Ignacio
Vázquez-Agra, Néstor
Antúnez-López, José Ramón
Bandín-Vilar, Enrique José
Sendón-García, Raquel
Busto-Iglesias, Manuel
Rodríguez-Bernaldo de Quirós, Ana
García-Quintanilla, Laura
González-Barcia, Miguel
Zarra-Ferro, Irene
Otero-Espinar, Francisco J.
Rey-Bretal, David
Lago-Quinteiro, José Ramón
Valdés-Cuadrado, Luis
Rábade-Castedo, Carlos
del Río-Garma, María Carmen
Crespo-Diz, Carlos
Delgado-Sánchez, Olga
Aguiar, Pablo
Barbeito-Castiñeiras, Gema
Pérez del Molino-Bernal, María Luisa
Trastoy-Pena, Rocío
Passannante, Rossana
Llop, Jordi
Pose-Reino, Antonio
Fernández-Ferreiro, Anxo
author_sort Castro-Balado, Ana
collection PubMed
description Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29).
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spelling pubmed-79992022021-03-28 Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection Castro-Balado, Ana Mondelo-García, Cristina Barbosa-Pereira, Letricia Varela-Rey, Iria Novo-Veleiro, Ignacio Vázquez-Agra, Néstor Antúnez-López, José Ramón Bandín-Vilar, Enrique José Sendón-García, Raquel Busto-Iglesias, Manuel Rodríguez-Bernaldo de Quirós, Ana García-Quintanilla, Laura González-Barcia, Miguel Zarra-Ferro, Irene Otero-Espinar, Francisco J. Rey-Bretal, David Lago-Quinteiro, José Ramón Valdés-Cuadrado, Luis Rábade-Castedo, Carlos del Río-Garma, María Carmen Crespo-Diz, Carlos Delgado-Sánchez, Olga Aguiar, Pablo Barbeito-Castiñeiras, Gema Pérez del Molino-Bernal, María Luisa Trastoy-Pena, Rocío Passannante, Rossana Llop, Jordi Pose-Reino, Antonio Fernández-Ferreiro, Anxo Pharmaceutics Article Inhaled administration of ethanol in the early stages of COVID-19 would favor its location on the initial replication sites, being able to reduce the progression of the disease and improving its prognosis. Before evaluating the efficacy and safety of this novel therapeutic strategy in humans, its characterization is required. The developed 65° ethanol formulation is stable at room temperature and protected from light for 15 days, maintaining its physicochemical and microbiological properties. Two oxygen flows have been tested for its administration (2 and 3 L/min) using an automated headspace gas chromatographic analysis technique (HS-GC-MS), with that of 2 L/min being the most appropriate one, ensuring the inhalation of an ethanol daily dose of 33.6 ± 3.6 mg/min and achieving more stable concentrations during the entire treatment (45 min). Under these conditions of administration, the formulation has proven to be safe, based on histological studies of the respiratory tracts and lungs of rats. On the other hand, these results are accompanied by the first preclinical molecular imaging study with radiolabeled ethanol administered by this route. The current ethanol formulation has received approval from the Spanish Agency of Medicines and Medical Devices for a phase II clinical trial for early-stage COVID-19 patients, which is currently in the recruitment phase (ALCOVID-19; EudraCT number: 2020-001760-29). MDPI 2021-03-05 /pmc/articles/PMC7999202/ /pubmed/33808025 http://dx.doi.org/10.3390/pharmaceutics13030342 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Castro-Balado, Ana
Mondelo-García, Cristina
Barbosa-Pereira, Letricia
Varela-Rey, Iria
Novo-Veleiro, Ignacio
Vázquez-Agra, Néstor
Antúnez-López, José Ramón
Bandín-Vilar, Enrique José
Sendón-García, Raquel
Busto-Iglesias, Manuel
Rodríguez-Bernaldo de Quirós, Ana
García-Quintanilla, Laura
González-Barcia, Miguel
Zarra-Ferro, Irene
Otero-Espinar, Francisco J.
Rey-Bretal, David
Lago-Quinteiro, José Ramón
Valdés-Cuadrado, Luis
Rábade-Castedo, Carlos
del Río-Garma, María Carmen
Crespo-Diz, Carlos
Delgado-Sánchez, Olga
Aguiar, Pablo
Barbeito-Castiñeiras, Gema
Pérez del Molino-Bernal, María Luisa
Trastoy-Pena, Rocío
Passannante, Rossana
Llop, Jordi
Pose-Reino, Antonio
Fernández-Ferreiro, Anxo
Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection
title Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection
title_full Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection
title_fullStr Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection
title_full_unstemmed Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection
title_short Development and Characterization of Inhaled Ethanol as a Novel Pharmacological Strategy Currently Evaluated in a Phase II Clinical Trial for Early-Stage SARS-CoV-2 Infection
title_sort development and characterization of inhaled ethanol as a novel pharmacological strategy currently evaluated in a phase ii clinical trial for early-stage sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999202/
https://www.ncbi.nlm.nih.gov/pubmed/33808025
http://dx.doi.org/10.3390/pharmaceutics13030342
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