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

Abstract

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.

Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial

“…Findings on IVM plasma concentrations are in agreement with human SARS-CoV-2 viral kinetic models identifying the need for high doses, but contradict those concerns stating that those drug concentrations would not be achievable at safe doses [5,22]. The extensive pattern of IVM distribution to lung tissue has been well characterized in cattle and pigs, with the later also achieving in nasopharyngeal tissue higher levels than plasma [16,23]. Considering that similar volumes of distribution have been reported for IVM in both cattle and humans and the systemic availability observed in this clinical trial, it is reasonable to estimate median IVM levels >395 ng/ g in lung tissue.…”

Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19

“…As a result, early in the infection, the viral load is reduced, preventing extensive viral replication, transmission, and disease aggravation. 41 …”

“…As a result, early in the infection, the viral load is reduced, preventing extensive viral replication, transmission, and disease aggravation. 41 No previous study has used ivermectin in a nanosuspension nasal spray. In this study we tried to decrease the viral load in the nose and nasopharynx in early COVID 19 patients by the direct action of an ivermectin nanosuspension nasal spray.…”

Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARS-CoV-2- Positive Patients

“…Since patient safety with multiple-day high-dose IVM regimens was shown [7], the design of further trials to confirm antiviral and clinical efficacy as well as to explore factors involved in oral bioavailability of the drug, seem to be warranted. Nasal spray administration is other attractive alternate route that would allow IVM accumulation in nasopharyngeal tissue [39].…”