Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model
High ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray (N-IVM-spray) administration may contribute to attaining high drug concentrations in nasopharyngeal (NP) tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performance of...
| Autores principales: | , , , , , , , , , , , , , , |
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| Formato: | Articulo Preprint |
| Lenguaje: | Español |
| Publicado: |
2020
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| Materias: | |
| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/124172 |
| Aporte de: |
| id |
I19-R120-10915-124172 |
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| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Español |
| topic |
Ciencias Médicas Pharmacokinetics Adverse effect Oral administration Ivermectin Respiratory tract Nostril Nasal spray Medicine Nasal administration Pharmacology |
| spellingShingle |
Ciencias Médicas Pharmacokinetics Adverse effect Oral administration Ivermectin Respiratory tract Nostril Nasal spray Medicine Nasal administration Pharmacology 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 Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model |
| topic_facet |
Ciencias Médicas Pharmacokinetics Adverse effect Oral administration Ivermectin Respiratory tract Nostril Nasal spray Medicine Nasal administration Pharmacology |
| description |
High ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray (N-IVM-spray) administration may contribute to attaining high drug concentrations in nasopharyngeal (NP) tissue, a primary site of virus entrance/replication. The safety and pharmacokinetic performance of a new N-IVM spray formulation in a piglet model were assessed. Crossbred piglets (10–12 kg) were treated with either one or two (12 h apart) doses of N-IVM-spray (2 mg, 1 puff/nostril) or orally (0.2 mg/kg). The overall safety of N-IVM-spray was assessed (clinical, haematological, serum biochemical determinations), and histopathology evaluation of the application site tissues performed. The IVM concentration profiles measured in plasma and respiratory tract tissues (nasopharynx and lungs) after the nasal spray treatment (one and two applications) were compared with those achieved after the oral administration. Animals tolerated well the novel N–IVM-spray formulation. No local/systemic adverse events were observed. After nasal administration, the highest IVM concentrations were measured in NP and lung tissues. Significant increases in IVM concentration profiles in both NP-tissue and lungs were observed after the 2-dose nasal administrations. The nasal/oral IVM concentration ratios in NP and lung tissues (at 6 h post-dose) markedely increased by repeating the spray application. The fast attainment of high and persistent IVM concentrations in NP tissue is the main advantage of the nasal over the oral route. These original results are encouraging to support the undertaking of further clinical trials to evaluate the safety/efficacy of the nasal IVM spray application in the treatment and/or prevention of COVID-19. |
| format |
Articulo Preprint |
| author |
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_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_sort |
Errecalde, Jorge Oscar |
| title |
Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model |
| title_short |
Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model |
| title_full |
Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model |
| title_fullStr |
Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model |
| title_full_unstemmed |
Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model |
| title_sort |
ivermectin repurposing for covid-19 therapy: safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model |
| publishDate |
2020 |
| url |
http://sedici.unlp.edu.ar/handle/10915/124172 |
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