{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:32:23Z","timestamp":1792794743784,"version":"4.5.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,2,13]],"date-time":"2019-02-13T00:00:00Z","timestamp":1550016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Wellcome Trust Strategic","award":["097377"],"award-info":[{"award-number":["097377"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"crossref"}]},{"name":"MRC Centre for Medical Mycology","award":["MR\/N006364\/1"],"award-info":[{"award-number":["MR\/N006364\/1"]}],"id":[{"id":"https:\/\/ror.org\/00vbzva31","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000882","name":"University of Aberdeen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000882","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Pharmacy Radboudumc"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Voriconazole is the mainstay of treatment for invasive aspergillosis in immunocompromised pediatric patients. Although Therapeutic Drug Monitoring (TDM) of voriconazole is recommended, it remains unknown if TDM-based dose adaptations result in target attainment. Patients &lt;19 years from two pediatric hematologic-oncology wards were retrospectively identified based on unexplained high voriconazole trough concentrations (Cmin &gt;\u00a06\u00a0mg\/l). Patient demographics, clinical characteristics, treatment, voriconazole dosing information, voriconazole Cmin before and after adjustment based on TDM were obtained. Twenty-one patients, median (range) age 7.0 (1.2\u201318.5) years, were identified in two centers. First Cmin (3.1\u00a0mg\/l [0.1\u201313.5]) was obtained after 3 days (1\u201327) of treatment. The median of all Cmin (n = 485, median 11 per patient) was 2.16\u00a0mg\/l (0.0 (undetectable)\u201328.0), with 24.1% of Cmin &lt; 1\u00a0mg\/l, 48.9% 1\u20134\u00a0mg\/l, 9.3% 4\u20136\u00a0mg\/l, and 17.7% &gt;\u00a06\u00a0mg\/l. Intrapatient variability was large (94.1% for IV, 88.5% for PO). Dose increases at Cmin &lt; 1\u00a0mg\/l resulted in an increased Cmin in 76.4%, with 60% between 1 and 4\u00a0mg\/l. Dose decreases at Cmin &gt;\u00a06\u00a0mg\/l resulted in a decreased Cmin in 80%, with 51% between 1 and 4\u00a0mg\/l. Overall, in 45% of the cases (33 out of 55 and 12 out of 45) therapeutic targets were attained after dose adjustment. Fifty-five percent of initial Cmin was outside the therapeutic target of 1\u20134\u00a0mg\/l, with multiple dose adaptations required to achieve therapeutic concentrations. Only 60% and 51% of dose adaptations following sub- and supra-therapeutic Cmin, respectively, did result in target attainment. Intensive and continuous TDM of voriconazole is a prerequisite for ensuring adequate exposure in pediatric patients.<\/jats:p>","DOI":"10.1093\/mmy\/myz006","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T15:13:02Z","timestamp":1547219582000},"page":"937-943","source":"Crossref","is-referenced-by-count":30,"title":["Impact of dose adaptations following voriconazole therapeutic drug monitoring in pediatric patients"],"prefix":"10.1093","volume":"57","author":[{"given":"Vincent J","family":"Lempers","sequence":"first","affiliation":[{"name":"Radboud university medical center, Department of Pharmacy and Radboud Institute for Health Sciences, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edm\u00e9","family":"Meuwese","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center, Department of Pharmacy, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelies M","family":"Mavinkurve-Groothuis","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Henriet","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Department of Pediatric Infectious Diseases & Immunology, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge M","family":"van der Sluis","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"},{"name":"Erasmus Medical Center-Sophia Children's Hospital, Department of Pediatric Haematology-Oncology, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidwien M","family":"Hanff","sequence":"additional","affiliation":[{"name":"Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adilia","family":"Warris","sequence":"additional","affiliation":[{"name":"MRC Centre for Medical Mycology, Aberdeen Fungal Group, Institute of Medical Sciences, University of Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit C P","family":"Koch","sequence":"additional","affiliation":[{"name":"Erasmus Medical Center, Department of Pharmacy, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger J","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Radboud university medical center, Department of Pharmacy and Radboud Institute for Health Sciences, Nijmegen, The Netherlands"},{"name":"Center of Expertise in Mycology Radboudumc\/CWZ, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,13]]},"reference":[{"key":"2019100317063503600_bib1","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/ciw326","article-title":"Practice guidelines for the diagnosis and management of aspergillosis: 2016 Update by the Infectious Diseases Society of America","volume":"63","author":"Patterson","year":"2016","journal-title":"Clin Infect Dis"},{"key":"2019100317063503600_bib2","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.cmi.2018.01.002","article-title":"Diagnosis and management of Aspergillus diseases: executive summary of the 2017 ESCMID-ECMM-ERS guideline","volume":"24","author":"Ullmann","year":"2018","journal-title":"Clin Microbiol Infect"},{"key":"2019100317063503600_bib3","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/FTD.0b013e31817b1a95","article-title":"Therapeutic drug monitoring of voriconazole","volume":"30","author":"Br\u00fcggemann","year":"2008","journal-title":"Ther Drug Monit"},{"key":"2019100317063503600_bib4","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1086\/524669","article-title":"Voriconazole tTherapeutic drug monitoring in patients with invasive mycoses improves efficacy and safety outcomes","volume":"46","author":"Pascual","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2019100317063503600_bib5","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s10156-011-0363-6","article-title":"Investigation and threshold of optimum blood concentration of voriconazole: a descriptive statistical meta-analysis","volume":"18","author":"Hamada","journal-title":"J Infect Chemother"},{"key":"2019100317063503600_bib6","doi-asserted-by":"crossref","first-page":"4793","DOI":"10.1128\/AAC.00626-12","article-title":"2012. 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