{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:49:53Z","timestamp":1791920993458,"version":"4.3.4"},"reference-count":78,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T00:00:00Z","timestamp":1667520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Favipiravir displays a rapid viral clearance, a high recovery rate and broad therapeutic safety; however, its oral administration was associated with systemic side effects in susceptible patients. Considering that the pulmonary route could provide a high drug concentration, and a safer application with less absorption into systemic circulation, it was aimed to elucidate whether favipiravir delivered via soft-mist inhaler has any deleterious effects on lung, liver and kidney tissues of healthy rats. Wistar albino rats of both sexes (n = 72) were placed in restrainers, and were given either saline or favipiravir (1, 2.5, 5 or 10 mg\/kg in 1 mL saline) by inhalation within 2 min for 5 consecutive days. On the 6th day, electrocardiographic recording was obtained, and cardiac blood and lung tissues were collected. Favipiravir did not alter cardiac rhythm, blood cell counts, serum levels of alanine transaminase, aspartate transaminase, blood urea nitrogen, creatinine, urea or uric acid, and did not cause any significant changes in the pulmonary malondialdehyde, myeloperoxidase activity or antioxidant glutathione levels. Our data revealed that pulmonary use of favipiravir via soft-mist inhaler enables a high local concentration compared to plasma without oxidative lung injury or cardiac or hepatorenal dysfunction.<\/jats:p>","DOI":"10.3390\/pharmaceutics14112375","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T09:23:37Z","timestamp":1667553817000},"page":"2375","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pulmonary Delivery of Favipiravir in Rats Reaches High Local Concentrations without Causing Oxidative Lung Injury or Systemic Side Effects"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6524-3535","authenticated-orcid":false,"given":"Ozlem","family":"Akbal-Dagistan","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3992-7335","authenticated-orcid":false,"given":"Mustafa","family":"Sevim","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Basic Medical Sciences, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyla Semiha","family":"Sen","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Basic Medical Sciences, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0695-5292","authenticated-orcid":false,"given":"Nur Sena","family":"Basarir","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7948-4340","authenticated-orcid":false,"given":"Meltem","family":"Culha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aybige","family":"Erturk","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"},{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istinye University, Istanbul 34010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan","family":"Fael","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0866-8796","authenticated-orcid":false,"given":"Engin","family":"Kaptan","sequence":"additional","affiliation":[{"name":"Section of Molecular Biology, Department of Biology, Faculty of Science, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7093-4744","authenticated-orcid":false,"given":"Serap","family":"Sancar","sequence":"additional","affiliation":[{"name":"Section of Molecular Biology, Department of Biology, Faculty of Science, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutfiye","family":"Mulazimoglu Durmusoglu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, School of Medicine, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0791-0165","authenticated-orcid":false,"given":"Berrak C.","family":"Yegen","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Medicine, Basic Medical Sciences, Marmara University, Istanbul 34854, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2243-6684","authenticated-orcid":false,"given":"Ayca","family":"Yildiz-Pekoz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology, Faculty of Pharmacy, Istanbul University, Istanbul 34116, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"key":"ref_1","first-page":"11","article-title":"The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak\u2013an update on the status","volume":"7","author":"Guo","year":"2020","journal-title":"Mil. 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