Ivermectin repurposing for COVID-19 therapy: Safety and pharmacokinetic assessment of a novel nasal spray formulation in a pig model (Argentina 2020-10-23) IVM nasal spray produced higher IVM concentration than oral IVM in piglets

TrumpLyftAlles | 4 points | Oct 26 2020 21:32:07

https://www.biorxiv.org/content/10.1101/2020.10.23.352831v1

[-] TrumpLyftAlles | 1 points | Oct 26 2020 21:32:39

Discussed here in /r/covid19.

[-] TrumpLyftAlles | 1 points | Oct 29 2020 17:06:54

Abstract
High ivermectin (IVM) concentrations suppress in vitro SARS-CoV-2 replication. Nasal IVM spray (NIVM 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 NIVM 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 NIVM-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 NIVM 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 NPtissue and lungs were observed after the 2 dose nasal administrations. The nasal/oral IVM concentration ratios in NP and lung tissues (at 6 h postdose) markedly 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.

[-] TrumpLyftAlles | 1 points | Oct 29 2020 17:08:53

A brief recap of this study in a Japan article.

After two nasal doses, a significant increase in IVM levels was observed in both the nasopharyngeal tissue and the lungs. Blood levels were kept low and no local or systemic adverse events were observed. Its effectiveness in humans against real viruses is uncertain.

[-] AdGroundbreaking2951 | 1 points | Nov 06 2020 18:03:52

Theoretical

High ivermectin (IVM) focuses stifle in vitro SARS-CoV-2 replication. Nasal IVM shower (NIVM splash) organization may add to accomplishing high medication focuses in nasopharyngeal (NP) tissue, an essential site of infection entrance/replication. The wellbeing and pharmacokinetic execution of another NIVM splash plan in a piglet model were evaluated. Crossbred piglets (10/12 kg) were treated with possibly a couple of (12 h separated) portions of N IVM splash (2 mg, 1 puff/nostril) or orally (0.2 mg/kg). The general wellbeing of NIVM-shower was surveyed (clinical, hematological, serum biochemical judgments), and histopathology assessment of the application site tissues performed. The IVM fixation profiles estimated in plasma and respiratory lot tissues (nasopharynx and lungs) after the nasal splash treatment (one and two applications) were contrasted and those accomplished after the oral organization.

Creatures endured well the novel NIVM shower definition. No nearby/foundational antagonistic functions were watched. After nasal organization, the most noteworthy IVM focuses were estimated in NP and lung tissues.

Critical expansions in IVM focus profiles in both NPtissue and lungs were seen after the 2 portion nasal organizations. The nasal/oral IVM focus proportions in NP and lung tissues (at 6 h postdose) uniquely expanded by rehashing the splash application. The quick fulfillment of high and constant IVM fixations in NP tissue is the fundamental favorable position of the nasal over the oral course. These unique outcomes are urging to help the endeavor of additional clinical preliminaries to assess the security/viability of the nasal IVM splash application in the treatment or potentially counteraction of COVID-19.