{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T17:45:43Z","timestamp":1792259143913,"version":"4.4.0"},"reference-count":12,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:00:00Z","timestamp":1792195200000},"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":["Eur J Clin Pharmacol"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Historical therapeutic drug monitoring (TDM) strategies for intravenous tobramycin in people with cystic fibrosis (pwCF) were developed in the pre-CFTR modulator era and relied predominantly on clearance-based monitoring to minimise toxicity. Contemporary pwCF demonstrate greater variability in body composition and clinical phenotype, potentially limiting the applicability of historical dosing approaches.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In December 2024, our adult cystic fibrosis centre implemented Bayesian-guided TDM (TDMx\n                      <jats:sup>\u00ae<\/jats:sup>\n                      ) for intravenous tobramycin. Two serum concentrations obtained during the first dosing interval were used to estimate maximum concentration (C\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      ), minimum concentration (C\n                      <jats:sub>\n                        <jats:italic>min<\/jats:italic>\n                      <\/jats:sub>\n                      ), and 24-hour area under the concentration-time curve (AUC\n                      <jats:sub>0\u2212\u200924<\/jats:sub>\n                      ), enabling model-informed dose individualisation. Outcomes were evaluated in 46 pwCF receiving intravenous tobramycin for pulmonary exacerbations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Prior to implementation, 74% of pwCF had not undergone formal dose review for more than three years. Following introduction of Bayesian monitoring, 98% received 24-hourly dosing compared with 33% under the historical protocol. Among pwCF with previous admissions, 72% required dose adjustment. Target C\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      (16\u201320\u00a0mg\/L) was achieved in 65.2% of participants, while only 17.4% achieved the target AUC\n                      <jats:sub>0\u2212\u200924<\/jats:sub>\n                      (&gt;\u200970\u00a0mg\u00b7h\/L); no participant exceeded the upper AUC target of 100\u00a0mg\u00b7h\/L. Thirteen pwCF who would previously have undergone dose reduction because of levels of &gt;1\u00a0mg\/L at 12\u00a0h demonstrated appropriate exposure on Bayesian assessment (mean C\n                      <jats:sub>\n                        <jats:italic>max<\/jats:italic>\n                      <\/jats:sub>\n                      17\u00a0mg\/L; mean AUC 74\u00a0mg\u00b7h\/L). No nephrotoxicity attributable to the protocol was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Bayesian-guided TDM was feasible, safe, and substantially altered tobramycin prescribing practice. It identified pwCF at risk of both inappropriate dose reduction and underexposure, supporting precision dosing in the evolving CF population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00228-026-04205-5","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T09:13:59Z","timestamp":1792228439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From historical dosing to precision dosing: Modernising tobramycin monitoring in people with cystic fibrosis"],"prefix":"10.1007","volume":"82","author":[{"given":"Ellie","family":"Johnson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Henderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Riddles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9669-0805","authenticated-orcid":false,"given":"Ieuan Edward Shepherd","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,17]]},"reference":[{"key":"4205_CR1","doi-asserted-by":"publisher","first-page":"102247","DOI":"10.1016\/j.pupt.2023.102247","volume":"82","author":"S Kuek","year":"2023","unstructured":"Kuek S, McCullagh A, Paul E, Armstrong D (2023) Real world outcomes of CFTR modulator therapy in Australian adults and children. 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