{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T17:00:42Z","timestamp":1773939642273,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res & Perspec"],"published-print":{"date-parts":[[2025,2]]},"abstract":"ABSTRACT<\/jats:title>The aim of this study was to evaluate safety, tolerability, and pharmacokinetics (PK) of single and multiple doses of a novel inhaled formulation of voriconazole (ZP\u2010059). In the single ascending dose part, 4 cohorts of 6 healthy subjects received one dose of inhaled voriconazole (5\u201340\u2009mg). In the multiple ascending dose part, 3 cohorts of 6 subjects with mild asthma received voriconazole 10\u2009mg twice daily [BID], 20\u2009mg BID or 40\u2009mg once daily. In the 2\u2010period crossover part, 16 subjects with mild to moderate asthma each received one dose of inhaled voriconazole 20\u2009mg and one dose of oral voriconazole 200\u2009mg. A bioanalytical method was developed and validated to simultaneously determine concentrations of voriconazole and its metabolite N\u2010oxide voriconazole in serum and sputum. Inhaled voriconazole was well tolerated with no treatment emergent adverse events (TEAEs) leading to treatment discontinuation. The PK profile of inhaled voriconazole showed rapid absorption, apparent greater than proportional increase in exposure with increasing dose, a consistent half\u2010life across dosing, and large clearance and volume of distribution. Following repeat administration limited accumulation was observed. Systemic exposure following inhaled voriconazole was much lower than following oral voriconazole. Serum data confirmed that voriconazole was extensively metabolized also when administered by inhalation. Sputum data following inhaled voriconazole were limited but demonstrated increasing exposure with increasing dose. The current study shows the newly developed dry powder inhaled formulation of voriconazole to be safe and well tolerated, providing a possible improved treatment approach for patients affected by allergic bronchopulmonary aspergillosis.<\/jats:p>Trial Registration:<\/jats:bold> ClinicalTrials.gov<\/jats:ext-link> ID: NCT04229303<\/jats:p>","DOI":"10.1002\/prp2.70064","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T11:39:12Z","timestamp":1738928352000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Phase I Study of the Safety, Tolerability, and Pharmacokinetics of Inhaled Voriconazole in Healthy Volunteers and Subjects With Stable Asthma"],"prefix":"10.1002","volume":"13","author":[{"given":"Giovanni","family":"Caponetti","sequence":"first","affiliation":[{"name":"Global Medical Office and R&D Zambon S.p.A. 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(MEU) The Langley Building Manchester UK"},{"name":"University of Manchester Manchester University NHS Hospital Trust Manchester UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2014-206291"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/mmy\/myy012"},{"issue":"8","key":"e_1_2_10_4_1","first-page":"936","article-title":"Aspergillus Hypersensitivity and Allergic Bronchopulmonary Aspergillosis in Patients With Bronchial Asthma: Systematic Review and Meta\u2010Analysis","volume":"13","author":"Agarwal R.","year":"2009","journal-title":"International Journal of Tuberculosis and Lung Disease"},{"issue":"24","key":"e_1_2_10_5_1","first-page":"00890","article-title":"Is the Prevalence of Allergic Bronchopulmonary Aspergillosis Greater in Severe Asthma?","volume":"2213","author":"Sehgal I. 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