{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T10:22:23Z","timestamp":1770978143039,"version":"3.50.1"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute of Health Research","doi-asserted-by":"crossref","award":["CS_08_08"],"award-info":[{"award-number":["CS_08_08"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["NICHD R01 HD070886"],"award-info":[{"award-number":["NICHD R01 HD070886"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC\/EC\n            <jats:sub>50<\/jats:sub>\n            ) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC\/EC\n            <jats:sub>50<\/jats:sub>\n            )\/15.4 predicted terminal galactomannan (\n            <jats:italic>P<\/jats:italic>\n            = 0.003), and a ratio of &gt;6 suggested a lower terminal galactomannan level (\n            <jats:italic>P<\/jats:italic>\n            = 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival.\n          <\/jats:p>","DOI":"10.1128\/aac.03023-15","type":"journal-article","created":{"date-parts":[[2016,2,2]],"date-time":"2016-02-02T04:44:41Z","timestamp":1454388281000},"page":"2336-2342","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy"],"prefix":"10.1128","volume":"60","author":[{"given":"Luc J.","family":"Huurneman","sequence":"first","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Neely","sequence":"additional","affiliation":[{"name":"Laboratory of Applied Pharmacokinetics and Bioinformatics, The Saban Research Institute, and Division of Pediatric Infectious Diseases, Children's Hospital Los Angeles, University of Southern California, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anette","family":"Veringa","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Docobo P\u00e9rez","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom"},{"name":"Unidad Intercentros de Enfermedades Infecciosas, Microbiolog\u00eda Cl\u00ednica y Medicina Preventiva, Hospital Universitario Virgen Macarena, Seville, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Ramos-Martin","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim J.","family":"Tissing","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Beatrix Children's Hospital, Department of Pediatric Oncology, Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Willem C.","family":"Alffenaar","sequence":"additional","affiliation":[{"name":"University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, the Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Department of Molecular and Clinical Pharmacology, Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tim.2010.02.004"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70017-8"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/525258"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-008-0574-7"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(03)80126-1"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/648679"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03820-14"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/598327"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt508"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02025-12"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00032-15"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1086\/588660"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/510535"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/496927"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir441"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2009.11.017"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31825c4ba6"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/524669"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0091270005283837"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/324620"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa020191"}],"container-title":["Antimicrobial 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