{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:37:20Z","timestamp":1791308240091,"version":"4.3.1"},"reference-count":62,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T00:00:00Z","timestamp":1675641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoF"],"abstract":"<jats:p>Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29\u20132.25] mg\/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg\/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.<\/jats:p>","DOI":"10.3390\/jof9020211","type":"journal-article","created":{"date-parts":[[2023,2,6]],"date-time":"2023-02-06T04:25:28Z","timestamp":1675657528000},"page":"211","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses"],"prefix":"10.3390","volume":"9","author":[{"given":"Lucas","family":"Perez","sequence":"first","affiliation":[{"name":"Department of Infectious and Tropical Diseases, Montpellier University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Corne","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Lapeyronie University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Pasquier","sequence":"additional","affiliation":[{"name":"CNRS, IRD, Montpellier University, MiVEGEC, Parasitology-Mycology Laboratory, CNR Leishmania, Montpellier University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6214-1613","authenticated-orcid":false,"given":"C\u00e9line","family":"Konecki","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, HERVI EA3801, University of Reims Champagne-Ardenne (URCA), Department of Pharmacology and Toxicology, Reims University Hospital, 51100 Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meriem","family":"Sadek","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Critical Care\u2014Cardiothoracic and Vascular Anesthesia\u2014Regional Expert ECMO Center, Arnaud de Villeneuve University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Le Bihan","sequence":"additional","affiliation":[{"name":"Department of Anesthesia and Intensive Care Unit, Saint-Eloi University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kada","family":"Klouche","sequence":"additional","affiliation":[{"name":"PhyMedExp, INSERM, CNRS, Montpellier University, Department of Intensive Care Medicine, Lapeyronie University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1198-2137","authenticated-orcid":false,"given":"Olivier","family":"Mathieu","sequence":"additional","affiliation":[{"name":"HSM, Montpellier University, Department of Pharmacology and Toxicology, Montpellier University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Reynes","sequence":"additional","affiliation":[{"name":"TRANSVIHMI Unit, Montpellier University\/IRD\/INSERM, Department of Infectious and Tropical Diseases, Montpellier University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1032-0879","authenticated-orcid":false,"given":"Yoann","family":"Cazaubon","sequence":"additional","affiliation":[{"name":"Institute Desbrest of Epidemiology and Public Health, INSERM, Montpellier University, Department of Pharmacology and Toxicology, Montpellier University Hospital, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern. 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