{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:19:52Z","timestamp":1787822392024,"version":"build-2784847793"},"reference-count":84,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:p>\n                    Intravenous tobramycin is a first\u2010line treatment for\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    <\/jats:styled-content>\n                    infection in people with cystic fibrosis (CF). Tobramycin exhibits concentration\u2010dependent activity; however, excess drug exposure can lead to nephrotoxicity and ototoxicity. While dosing typically targets serum peak (C\n                    <jats:sub>max<\/jats:sub>\n                    ) and trough (C\n                    <jats:sub>min<\/jats:sub>\n                    ) concentrations, the area under the concentration\u2013time curve over 24\u2009h (AUC\n                    <jats:sub>24<\/jats:sub>\n                    ) is also used to guide therapy. However, optimal exposure targets remain unclear, leading to variability in clinical practice and guidelines. This review aimed to determine the target tobramycin concentrations and exposure (C\n                    <jats:sub>max<\/jats:sub>\n                    , C\n                    <jats:sub>min<\/jats:sub>\n                    , AUC\n                    <jats:sub>24<\/jats:sub>\n                    ) associated with clinical efficacy (lung function improvement) and\/or toxicity (nephrotoxicity, ototoxicity) in CF. Four databases (PubMed, Medline, Embase and Cochrane) were searched and identified studies involving CF patients receiving intravenous tobramycin, recorded tobramycin drug concentration\/exposure alongside either clinical efficacy or drug\u2010related toxicity outcomes. Studies with \u226410 patients,\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies and reviews were excluded. The Newcastle\u2013Ottawa Scale was used to assess risk of bias. A meta\u2010analysis was not conducted. Twenty\u2010six studies were included; efficacy was reported in 17, nephrotoxicity in 16 and ototoxicity in 17. Both C\n                    <jats:sub>max<\/jats:sub>\n                    and AUC\n                    <jats:sub>24<\/jats:sub>\n                    were associated with efficacy, with AUC\n                    <jats:sub>24<\/jats:sub>\n                    being the more reliable predictor. C\n                    <jats:sub>min<\/jats:sub>\n                    and AUC\n                    <jats:sub>24<\/jats:sub>\n                    were associated with toxicity. Only 11 studies reported AUC\n                    <jats:sub>24<\/jats:sub>\n                    , and the overall quality of evidence was poor (21 with medium\/high risk of bias, 5 low bias). Current therapeutic C\n                    <jats:sub>max<\/jats:sub>\n                    (20\u201340\u2009mg\/L) and C\n                    <jats:sub>min<\/jats:sub>\n                    (&lt;1\u2009mg\/L) targets remain appropriate. Evidence suggests AUC\n                    <jats:sub>24<\/jats:sub>\n                    \u2010guided dosing for improved efficacy and safety; however, further research is needed to confirm the optimal AUC\n                    <jats:sub>24<\/jats:sub>\n                    target (80\u2013120\u2009mg\/L\u00b7h).\n                  <\/jats:p>","DOI":"10.1002\/bcp.70637","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T11:33:06Z","timestamp":1781177586000},"page":"3017-3026","source":"Crossref","is-referenced-by-count":0,"title":["Tobramycin pharmacokinetic and pharmacodynamic targets in people with cystic fibrosis"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9507-2497","authenticated-orcid":false,"given":"Kiera H.","family":"Harwood","sequence":"first","affiliation":[{"name":"Department of Paediatrics The University of Melbourne  Melbourne Victoria Australia"},{"name":"Murdoch Children's Research Institute 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