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

{ 'indexed': {'date-parts': [[2024, 4, 15]], 'date-time': '2024-04-15T23:13:53Z', 'timestamp': 1713222833183}, 'reference-count': 41, 'publisher': 'Springer Science and Business Media LLC', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2020, 10, 13]], 'date-time': '2020-10-13T00:00:00Z', 'timestamp': 1602547200000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2020, 10, 13]], 'date-time': '2020-10-13T00:00:00Z', 'timestamp': 1602547200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [ { 'DOI': '10.13039/501100004435', 'name': 'Universidad de Navarra', 'doi-asserted-by': 'publisher'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>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\xa0mg/kg), higher dose (110–140\xa0mg/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\xa0g/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 C<jats:sub>max</jats:sub> 86.2\xa0ng/ml vs. 26.2\xa0' 'ng/ml in the lower dose group and 152\xa0ng/ml vs. 51.8\xa0ng/ml in the higher dose group). ' 'All subjects had detectable ivermectin concentrations in the lungs at seven days post ' 'intervention, up to 524.3\xa0ng/g for high-dose male and 27.3\xa0ng/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.</jats:p>', 'DOI': '10.1038/s41598-020-74084-y', 'type': 'journal-article', 'created': { 'date-parts': [[2020, 10, 13]], 'date-time': '2020-10-13T10:05:00Z', 'timestamp': 1602583500000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 29, 'title': 'Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof of concept, ' 'dose-ranging study in rats', 'prefix': '10.1038', 'volume': '10', 'author': [ {'given': 'Carlos', 'family': 'Chaccour', 'sequence': 'first', 'affiliation': []}, {'given': 'Gloria', 'family': 'Abizanda', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ángel', 'family': 'Irigoyen-Barrio', 'sequence': 'additional', 'affiliation': []}, {'given': 'Aina', 'family': 'Casellas', 'sequence': 'additional', 'affiliation': []}, {'given': 'Azucena', 'family': 'Aldaz', 'sequence': 'additional', 'affiliation': []}, {'given': 'Fernando', 'family': 'Martínez-Galán', 'sequence': 'additional', 'affiliation': []}, {'given': 'Felix', 'family': 'Hammann', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ana Gloria', 'family': 'Gil', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2020, 10, 13]]}, 'reference': [ { 'key': '74084_CR1', 'doi-asserted-by': 'publisher', 'first-page': 'JC63', 'DOI': '10.7326/ACPJ202006160-063', 'volume': '172', 'author': 'P Yang', 'year': '2020', 'unstructured': 'Yang, P., Tekwani, S. & Martin, G. 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