Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats
Ivermectin is a widely used antiparasitic drug with known efcacy against several single-strain RNA viruses. Recent data shows signifcant 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...
| Main Authors: | , , , , , , , |
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
| Published: |
2023
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| Online Access: | https://hdl.handle.net/10171/67181 |
| _version_ | 1793400403223642112 |
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| author | Chaccour, C.J. (Carlos J.) Abizanda-Sarasa, G. (Gloria) Irigoyen-Barrio, A. (Angel) Casellas, A. (Aina) Aldaz, A. (Azucena) Martinez-Galan, F. (Fernando) Hammann, F. (Felix) Gil, A.G. (Ana Gloria) |
| author_facet | Chaccour, C.J. (Carlos J.) Abizanda-Sarasa, G. (Gloria) Irigoyen-Barrio, A. (Angel) Casellas, A. (Aina) Aldaz, A. (Azucena) Martinez-Galan, F. (Fernando) Hammann, F. (Felix) Gil, A.G. (Ana Gloria) |
| author_sort | Chaccour, C.J. (Carlos J.) |
| collection | DSpace |
| description | Ivermectin is a widely used antiparasitic drug with known efcacy against several single-strain RNA
viruses. Recent data shows signifcant 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 profle including behavioral and weight monitoring, full blood count, biochemistry,
necropsy and histological examination of the lungs was conducted. The pharmacokinetic profle
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. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-67181 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2023 |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-671812024-01-24T09:36:38Z Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats Chaccour, C.J. (Carlos J.) Abizanda-Sarasa, G. (Gloria) Irigoyen-Barrio, A. (Angel) Casellas, A. (Aina) Aldaz, A. (Azucena) Martinez-Galan, F. (Fernando) Hammann, F. (Felix) Gil, A.G. (Ana Gloria) Ivermectin is a widely used antiparasitic drug with known efcacy against several single-strain RNA viruses. Recent data shows signifcant 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 profle including behavioral and weight monitoring, full blood count, biochemistry, necropsy and histological examination of the lungs was conducted. The pharmacokinetic profle 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. 2023-08-31T08:01:29Z 2023-08-31T08:01:29Z 2020 info:eu-repo/semantics/article https://hdl.handle.net/10171/67181 eng info:eu-repo/semantics/openAccess application/pdf |
| spellingShingle | Chaccour, C.J. (Carlos J.) Abizanda-Sarasa, G. (Gloria) Irigoyen-Barrio, A. (Angel) Casellas, A. (Aina) Aldaz, A. (Azucena) Martinez-Galan, F. (Fernando) Hammann, F. (Felix) Gil, A.G. (Ana Gloria) Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats |
| title | Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats |
| title_full | Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats |
| title_fullStr | Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats |
| title_full_unstemmed | Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats |
| title_short | Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats |
| title_sort | nebulized ivermectin for covid-19 and other respiratory diseases, a proof of concept, dose-ranging study in rats |
| url | https://hdl.handle.net/10171/67181 |
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