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

ERRECALDE, JORGE; LIFSCHITZ, ADRIAN; VECCHIOLI, GRACIELA; CEBALLOS, LAURA; ERRECALDE, FRANCISCO; BALLENT, MARIANA; MARÍN, GUSTAVO; DANIELE, MARTÍN; TURIC, ESTEBAN; SPITZER, EDUARDO; TONEGUZZO, FERNANDO; GOLD, SILVIA; KROLEWIECKI, ALEJANDRO; ALVAREZ, LUIS; LANUSSE, CARLOS

JOURNAL OF PHARMACEUTICAL SCIENCES

JOHN WILEY & SONS INC

Lugar: New York; Año: 2021

0022-3549

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 innasopharyngeal tissue, a primary site of virus entrance/replication. The safety and pharmacokineticperformances of a novel IVM spray formulation were assessed in a pig model. Piglets received IVM eitherorally (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 andrespiratory tract tissues after the nasal spray were compared with those achieved after the oraladministration. Animals tolerated well the nasal spray formulation. No local/systemic adverse eventswere 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 tissuesmarkedly increased by repeating (12 h apart) the spray application. The fast attainment of high andpersistent IVM concentrations in nasopharyngeal tissue is the main advantage of the nasal over the oralroute. 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