{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:56:26Z","timestamp":1791860186951,"version":"4.3.4"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T00:00:00Z","timestamp":1747008000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pharmacol Toxicol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFN\u03b1 is both effective and safe for treating respiratory infections. However, IFN\u03b1 has a short half-life and is rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation is a common strategy to extend the duration of drug action. PegIFN\u03b1-2b is a long-acting interferon formed by the covalent binding of 40\u00a0kDa Y-shaped branched PEG with recombinant human IFN\u03b1-2b. This study aimed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics of nebulized PegIFN\u03b1-2b in healthy adult subjects, providing guidance for further clinical investigations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This study employed a randomized, controlled clinical trial design with a total of 18 healthy adult subjects enrolled. Participants were randomly assigned in a 1:1:1 ratio to three groups. Treatment group 1 and group 2 received 90\u00a0\u00b5g and 180\u00a0\u00b5g of nebulized PegIFN\u03b1-2b, respectively, while the control group was administered a combination of 180\u00a0\u00b5g PegIFN\u03b1-2b and 15\u00a0mg inhalable Ambroxol Hydrochloride solution, all in a single dose. Safety, tolerability, and blood drug concentration were assessed, along with blood neopterin levels for pharmacokinetic and pharmacodynamic evaluation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The incidence of adverse events (AEs) was 38.9% (7\/18) with no significant difference among the groups (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.05). AEs included anemia (<jats:italic>N<\/jats:italic>\u2009=\u20095) and leukopenia (<jats:italic>N<\/jats:italic>\u2009=\u20092), predominantly of grade 1 severity (6\/7), with no severe events. Blood PegIFN\u03b1-2b concentrations were below detection limits in most subjects, except one in treatment group 2. Neopterin levels were generally low in treatment group 1 and the control group, with slightly higher observed in most subjects of treatment group 2, but differences were not significant (<jats:italic>P<\/jats:italic>\u2009&gt;\u20090.05).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Nebulized PegIFN\u03b1-2b at doses of 90\u00a0\u00b5g and 180\u00a0\u00b5g showed acceptable safety and tolerability. Minimal systemic absorption was observed following inhalation. Further studies are needed to explore its potential, especially in patients with lower respiratory tract infections.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical trial registration<\/jats:title>\n            <jats:p>ChiCTR2300074909, retrospectively registered in <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.chictr.org.cn\/\" ext-link-type=\"uri\">https:\/\/www.chictr.org.cn\/<\/jats:ext-link> at 20 August 2023.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40360-025-00937-9","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T13:31:02Z","timestamp":1747056662000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon \u03b1-2b in healthy adults: a randomized phase 1 trial"],"prefix":"10.1186","volume":"26","author":[{"given":"Wenqi","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanneng","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changjuan","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weibing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinchao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,12]]},"reference":[{"key":"937_CR1","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1056\/NEJMra074111","volume":"358","author":"JP Mizgerd","year":"2008","unstructured":"Mizgerd JP. 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