{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:24:54Z","timestamp":1788351894752,"version":"build-2803163510"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Longitudinal evidence on repeated voriconazole therapeutic drug monitoring (TDM) in selected hospitalised patients is limited. We examined factors associated with out-of-range exposure and described concentration changes after dose adjustment in hospitalised patients undergoing repeated TDM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective, single-centre, longitudinal cohort study included hospitalised adults who received voriconazole and contributed at least three valid TDM episodes. Trough concentrations were classified as subtherapeutic (&amp;lt;1.0\u00a0\u03bcg\/mL), in range (1.0\u20135.0\u00a0\u03bcg\/mL), or supratherapeutic (&amp;gt;5.0\u00a0\u03bcg\/mL). Bayesian mixed-effects logistic regression with weakly informative priors and patient-level random intercepts identified factors associated with each direction of out-of-range exposure. Adjacent TDM pairs with a documented dose change were analysed for return to range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 140 patients contributed 497 episodes; 72 (14.5%) were subtherapeutic and 145 (29.2%) supratherapeutic. In the 445-episode complete-case models, subtherapeutic exposure was associated with rifampin-like inducer co-administration (OR 16.48, 95% CrI 2.38\u2013139.44) and lower daily dose (OR 0.45 per 100\u00a0mg, 95% CrI 0.29\u20130.66), whereas supratherapeutic exposure was associated with the\n                      <jats:italic>CYP2C19<\/jats:italic>\n                      poor-metaboliser phenotype (OR 5.24, 95% CrI 1.76\u201316.66), higher log-CRP (OR 1.69, 95% CrI 1.23\u20132.40), and higher total bilirubin (OR 1.09 per 10\u00a0\u03bcmol\/L, 95% CrI 1.03\u20131.15). Concentrations returned to range after 7 of 12 (58.3%) clinically concordant dose increases, but after only 26 of 75 (34.7%) clinically concordant dose decreases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In hospitalised patients undergoing repeated voriconazole TDM, the factors associated with subtherapeutic and supratherapeutic exposure differed by direction. After dose reduction, supratherapeutic concentrations frequently did not return to range; this descriptive pattern is compatible with several contributors, including resampling before a new steady state and voriconazole\u2019s nonlinear metabolism. These findings may help clinicians interpret repeated TDM results in complex inpatient settings.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1867435","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T12:11:40Z","timestamp":1788351100000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Repeated voriconazole therapeutic drug monitoring in hospitalised patients: a real-world cohort study of out-of-range exposure and concentration response to dose adjustment"],"prefix":"10.3389","volume":"17","author":[{"given":"Tian","family":"He","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Shenzhen Third People's Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Shenzhen Technology University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limian","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Third People's Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmei","family":"Qiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Third People's Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Third People's Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Third People's Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaona","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Third People's Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shenzhen Third People's Hospital, Second Affiliated Hospital of Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases","place":["Shenzhen, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1093\/jac\/dkt508","article-title":"Therapeutic drug monitoring (TDM) of antifungal agents: guidelines from the British Society for Medical Mycology","volume":"69","author":"Ashbee","year":"2014","journal-title":"J. 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