{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T03:59:10Z","timestamp":1788667150219,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Pharmaceutical Technology and Biopharmacy of the University of Groningen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background:\u00a0Pseudomonas aeruginosa (Pa) is the predominant pulmonary pathogen in persons with Cystic Fibrosis (CF). Nebulization with tobramycin or colistin is mostly applied but has a significant treatment burden. Dry powder (DP) inhalation may offer an attractive alternative. The aim of this study was to assess local tolerability and the systemic pharmacokinetic parameters of increasing doses of dry powder tobramycin. Methods: This was a local tolerability and pharmacokinetic evaluation pilot study DP tobramycin of three different doses inhaled through the Cyclops (30, 60, 120 mg) in ten persons with CF, aged 6\u201318 years, compared to nebulization of tobramycin solution. Results: Both nebulization of tobramycin in solution and inhalation of dry powder tobramycin were well tolerated. None of the participants showed a significant drop in FEV1 after inhalation. The only two adverse events were cough and bad taste in, respectively, 20% and 13% of all inhalations, compared to 10% cough and 60% bad taste with nebulization. Systemic tobramycin levels were not detected after 30 mg, detected only in 10% after 60 mg and in 30% after 120 mg, compared to 80% after nebulization. Conclusions: Inhalation of dry powder tobramycin using the Cyclops is well tolerated, with no significant drop in FEV1, and only mild adverse events of cough and bad taste. We found only a few detectable systemic tobramycin levels after inhalation of dry powder tobramycin. We recommend that future studies should focus on the relation between dose and inhaler resistance in different pediatric age groups.<\/jats:p>","DOI":"10.3390\/pharmaceutics17030347","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:22:52Z","timestamp":1741350172000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Tolerability and Pharmacokinetic Evaluation of Inhaled Dry Powder Tobramycin in Children with Cystic Fibrosis"],"prefix":"10.3390","volume":"17","author":[{"given":"Anne M.","family":"Akkerman-Nijland","sequence":"first","affiliation":[{"name":"Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children\u2019s Hospital, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-1905","authenticated-orcid":false,"given":"Paul","family":"Hagedoorn","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart L.","family":"Rottier","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children\u2019s Hospital, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0897-5673","authenticated-orcid":false,"given":"Floris","family":"Grasmeijer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 Groningen, The Netherlands"},{"name":"PureIMS B.V., 9301 Roden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7901-8198","authenticated-orcid":false,"given":"Henderik (Erik) W.","family":"Frijlink","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8409-9316","authenticated-orcid":false,"given":"Mathijs","family":"van Luin","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University Medical Center Utrecht, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"ter Weijden","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University Medical Center Utrecht, 3584 Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Merkus","sequence":"additional","affiliation":[{"name":"Amalia Children\u2019s Hospital, Radboud University Medical Center, 6525 Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-4789","authenticated-orcid":false,"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy & Pharmacology, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5638-9260","authenticated-orcid":false,"given":"Onno W.","family":"Akkerman","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Diseases and Tuberculosis, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard H.","family":"Koppelman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pulmonology and Pediatric Allergology, Beatrix Children\u2019s Hospital, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1542\/pir.22.8.257","article-title":"Cystic fibrosis","volume":"22","author":"David","year":"2001","journal-title":"Pediatr. 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