Ivermectin: a mini-review.

Introduction: Avermectins are common antiparasitic drugs, derived from Streptomyces bacteria that exhibit activity against arthropods and nematodes. Ivermectin, an avermectin derivative, is used as a treatment for parasitic infections in humans and domesticated animals.Discussion: Ivermectin's mechanism of action involves binding to ligand-gated ion channel receptors including glutamate, GABA, and glycine, resulting in parasitic paralysis and death. Due to varying expression of these ion channel receptors in vertebrate species, ivermectin toxicity is rarely reported in mammals. Ivermectin is also a substrate for P-glycoprotein, which limits its neurological toxicity in humans. Genetic polymorphisms in P-glycoprotein or coadministration of P-glycoprotein inhibitors may increase the neurotoxicity of ivermectin. Other toxic effects of ivermectin after therapeutic oral use include edema, rash, headache, and ocular complaints. Most of these effects are mild and short in duration. Ivermectin exhibits antiviral effects in-vitro at very high concentrations. This has led to suggestions of ivermectin as a potential treatment for SARS-CoV-2 (COVID-19) infection, although the drug's pharmacokinetic parameters reduce the likelihood that high concentrations of the drug can be achieved in-vivo.Conclusion: Due to concern for adverse events, specifically neurotoxicity, as well as a paucity of supporting evidence, the use of ivermectin as a routine treatment or preventive measure for COVID-19 infection is not recommended at this time.

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

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.

Ecotoxic response of nematodes to ivermectin, a potential anti-COVID-19 drug treatment.

At the end of March 2020, ivermectin was confirmed as a drug for COVID-19 treatment. A significant amount of ivermectin could deposit into sediments of the semi-closed Mediterranean Sea, where three European COVID-19 epicenters are located: Italy, Spain, and France. Meiobenthic nematodes were exposed to three ivermectin doses (1.8 ng.g-1, 9 ng.g-1, and 18 ng.g-1) for 10 days. Ivermectin caused a great reduction in abundance. However, the diversity indices decreased only at high doses. Ivermectin disadvantaged the 1B-Cr-Id functional type (non-selective deposit feeders and nematodes with circular or indistinct amphids) and benefited the 2A-REL-Sp type (epistrate feeders and nematodes with rounded or elongated loop amphids). Thus, Trophic Diversity and Amphideal Diversity index values increased with sedimentary ivermectin enrichment. Large amphideal foveas were more efficient for 2A-REL-Sp nematodes to avoid ivermectin. The responses of the functional type 2A-REL-Sp and corresponding taxa predict post-COVID-19 environmental concerns and the bioaccumulation of ivermectin in seafoods.