Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats.

Chaccour, Carlos; Abizanda, Gloria; Irigoyen-Barrio, Ángel; Casellas, Aina; Aldaz, Azucena; Martínez-Galán, Fernando; Hammann, Felix; Gil, Ana Gloria (2020). Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats. Scientific reports, 10(1), p. 17073. 10.1038/s41598-020-74084-y

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Ivermectin is a widely used antiparasitic drug with known efficacy against several single-strain RNA viruses. Recent data shows significant reduction of SARS-CoV-2 replication in vitro by ivermectin concentrations not achievable with safe doses orally. Inhaled therapy has been used with success for other antiparasitics. An ethanol-based ivermectin formulation was administered once to 14 rats using a nebulizer capable of delivering particles with alveolar deposition. Rats were randomly assigned into three target dosing groups, lower dose (80-90 mg/kg), higher dose (110-140 mg/kg) or ethanol vehicle only. A toxicology profile including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profile of ivermectin in plasma and lungs was determined in all animals. There were no relevant changes in behavior or body weight. There was a delayed elevation in muscle enzymes compatible with rhabdomyolysis, that was also seen in the control group and has been attributed to the ethanol dose which was up to 11 g/kg in some animals. There were no histological anomalies in the lungs of any rat. Male animals received a higher ivermectin dose adjusted by adipose weight and reached higher plasma concentrations than females in the same dosing group (mean Cmax 86.2 ng/ml vs. 26.2 ng/ml in the lower dose group and 152 ng/ml vs. 51.8 ng/ml in the higher dose group). All subjects had detectable ivermectin concentrations in the lungs at seven days post intervention, up to 524.3 ng/g for high-dose male and 27.3 ng/g for low-dose females. nebulized ivermectin can reach pharmacodynamic concentrations in the lung tissue of rats, additional experiments are required to assess the safety of this formulation in larger animals.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Clinic of General Internal Medicine

UniBE Contributor:

Hammann, Felix

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2045-2322

Language:

English

Submitter:

Christine Baumgartner

Date Deposited:

03 Nov 2020 16:10

Last Modified:

10 Mar 2021 08:00

Publisher DOI:

10.1038/s41598-020-74084-y

PubMed ID:

33051517

BORIS DOI:

10.7892/boris.147764

URI:

https://boris.unibe.ch/id/eprint/147764

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