{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:54:55Z","timestamp":1793829295628,"version":"4.6.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Posaconazole is used for the prophylaxis and treatment of invasive fungal infections in critically ill patients. Standard dosing was shown to result in adequate attainment of the prophylaxis Cmin target (0.7\u2005mg\/L) but not of the treatment Cmin target (1.0\u2005mg\/L).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To provide an optimized posaconazole dosing regimen for IV treatment of patients with invasive pulmonary aspergillosis in the ICU.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A population pharmacokinetics (popPK) model was developed using data from the POSA-FLU PK substudy (NCT03378479). Monte Carlo simulations were performed to assess treatment Cmin and AUC0\u201324 PTA. PTA \u226590% was deemed clinically acceptable. PopPK modelling and simulation were performed using NONMEM 7.5.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-one patients with intensive PK sampling were included in the PK substudy, contributing 532 posaconazole plasma concentrations. The popPK of IV posaconazole was best described by a two-compartment model with linear elimination. Interindividual variability was estimated on clearance and volume of distribution in central and peripheral compartments. Posaconazole peripheral volume of distribution increased with bodyweight. An optimized loading regimen of 300\u2005mg q12h and 300\u2005mg q8h in the first two treatment days achieved acceptable PTA by Day 3 in patients &amp;lt;100\u2005kg and \u2265100\u2005kg, respectively. A maintenance regimen of 400\u2005mg q24h ensured \u226590% Cmin PTA, whereas the standard 300\u2005mg q24h was sufficient to achieve the AUC0\u201324 target throughout 14\u2005days, irrespective of bodyweight.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We have defined a convenient, optimized IV posaconazole dosing regimen that was predicted to attain the treatment target in critically ill patients with invasive aspergillosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae160","type":"journal-article","created":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T17:13:07Z","timestamp":1717434787000},"page":"1645-1656","source":"Crossref","is-referenced-by-count":3,"title":["Dosing of IV posaconazole to treat critically ill patients with invasive pulmonary aspergillosis: a population pharmacokinetics modelling and simulation study"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5708-9497","authenticated-orcid":false,"given":"Omar","family":"Elkayal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1501-3045","authenticated-orcid":false,"given":"Beatrijs","family":"Mertens","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, KU Leuven , Leuven , Belgium"},{"name":"Pharmacy Department, UZ Leuven , Leuven , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5983-3897","authenticated-orcid":false,"given":"Joost","family":"Wauters","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit, UZ Leuven , Leuven , Belgium"},{"name":"Laboratory for Clinical Infectious and 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Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8600-9860","authenticated-orcid":false,"given":"Paul E","family":"Verweij","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Radboudumc, CWZ Center of Expertise for Mycology, Radboud University Medical Center , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-725X","authenticated-orcid":false,"given":"Roger J","family":"Br\u00fcggemann","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Radboud Institute for Medical Innovation, Radboud University Medical Center, Nijmegen and Radboudumc, CWZ Center of Expertise for Mycology, Radboud University Medical Center , Nijmegen , The 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