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

Errecalde et al., Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017

Errecalde et al., Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray Formulation in a Pig Model, Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017

Jan 2021 Source PDF

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Animal study of a novel spray formulation of ivermectin, showing an advantage of the spray formulation in terms of fast attainment of high and persistent ivermectin concentrations in nasopharyngeal tissue.

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Errecalde et al., 23 Jan 2021, peer-reviewed, 15 authors.

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

Jorge Errecalde, Adrian Lifschitz, Graciela Vecchioli, Laura Ceballos, Francisco Errecalde, Mariana Ballent, Gustavo Marín, Martín Daniele, Esteban Turic, Eduardo Spitzer, Fernando Toneguzzo, Silvia Gold, Alejandro Krolewiecki, Luis Alvarez, Carlos Lanusse

Journal of Pharmaceutical Sciences, doi:10.1016/j.xphs.2021.01.017

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 IVMspray 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.

Author Contributions J. Errecalde. Protocol design, IVM spray design. Animal phase work (Spray administration and sampling). Data analysis. Overall integration/discussion of the data. Manuscript writing. A. Lifschitz. Protocol design. HPLC analysis. PK data analysis. Overall integration/discussion of the data. Manuscript writing. G. Vecchioli.

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