{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:54:30Z","timestamp":1791266070611,"version":"4.1.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"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. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background and objective<\/jats:title>\n                    <jats:p>Isavuconazole is the first-line option for the treatment of invasive aspergillosis and mucormycosis. However, it has large pharmacokinetic (PK) variabilities, and suboptimal exposure is concerned. This study aimed to develop an isavuconazole population pharmacokinetic (PPK) library that contributes to model-informed precision dosing (MIPD) and dose optimization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Following a systematic literature search and study inclusion, a library of isavuconazole PPK models was developed. The model characteristics and parameters estimated were extracted and compared. The AUC distributions at steady status across different models were compared, and the effects of covariates on PK parameters were analyzed. The model library was used to estimate target achievement with the PK\/PD target of AUC\/MIC 33 for Aspergillus through Monte Carlo simulations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 955 unduplicated records were initially identified from PubMed, Web of Science, and Embase. After screening and eligibility assessment, 14 studies were ultimately included in the model library. The quality scores of the included studies ranged from 35 to 45. The included PPK models had high reporting quality and covered a diversity of patients, with the two-compartment model being the most common. The total clearance of isavuconazole ranged from 1.33\u20135.34\u202fL\/h. Body weight, body surface area (BSA), body mass index (BMI), albumin levels, and liver function markers were the most common significant covariates, and their overall impact met the clinically significant criteria. The simulation results indicate that for a susceptive threshold of MIC 1\u202fmg\/L, most models (11\/14) achieved PTA over 90%, while dose optimization may be required for critically ill patients, hematological patients and patients with abnormal covariates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study successfully developed a PPK library for isavuconazole, which would support the precision dosing of isavuconazole.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1930025","type":"journal-article","created":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:27Z","timestamp":1791264087000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetic model library for isavuconazole: development and quality control"],"prefix":"10.3389","volume":"17","author":[{"given":"Qing","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Research Center for Clinical Pharmacy, College of Pharmaceutical Science, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Affiliated Xiaoshan Hospital, Hangzhou Normal University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieqiong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renai","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, First Affiliated Hospital of Wenzhou Medical University","place":["Wenzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University","place":["Hangzhou, China"]},{"name":"Research Center for Clinical Pharmacy, College of Pharmaceutical Science, Zhejiang University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"ref1","year":"2025"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"571.e1","DOI":"10.1016\/j.cmi.2016.01.017","article-title":"EUCAST technical note on isavuconazole breakpoints for aspergillus, itraconazole breakpoints for Candida and updates for the antifungal susceptibility testing method documents","volume":"22","author":"Arendrup","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e0029021","DOI":"10.1128\/aac.00290-21","article-title":"Safety, tolerability, and population pharmacokinetics of intravenous and Oral Isavuconazonium Sulfate in Pediatric patients","volume":"65","author":"Arrieta","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1093\/jac\/dkae088","article-title":"Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions","volume":"79","author":"Bergmann","year":"2024","journal-title":"J. Antimicrob. Chemother."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"5756","DOI":"10.3390\/jcm11195756","article-title":"Variability of isavuconazole trough concentrations during longitudinal therapeutic drug monitoring","volume":"11","author":"Bolcato","year":"2022","journal-title":"J. Clin. Med."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"7559","DOI":"10.2147\/idr.S434622","article-title":"Population pharmacokinetics of Isavuconazole in adult: a systematic review","volume":"16","author":"Chen","year":"2023","journal-title":"Infect Drug Resist."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.3390\/pharmaceutics13122099","article-title":"Population pharmacokinetics and pharmacodynamic target attainment of isavuconazole against aspergillus fumigatus and aspergillus flavus in adult patients with invasive fungal diseases: should therapeutic drug monitoring for isavuconazole be considered as mandatory as for the other mold-active azoles?","volume":"13","author":"Cojutti","year":"2021","journal-title":"Pharmaceutics"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e02629","DOI":"10.1128\/AAC.02629-18","article-title":"No dose adjustment for Isavuconazole based on age or sex","volume":"63","author":"Desai","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"e01034","DOI":"10.1128\/AAC.01034-17","article-title":"Exposure-response relationships for Isavuconazole in patients with invasive aspergillosis and other filamentous Fungi","volume":"61","author":"Desai","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"5483","DOI":"10.1128\/aac.02819-15","article-title":"Population pharmacokinetics of Isavuconazole from phase 1 and phase 3 (SECURE) trials in adults and target attainment in patients with invasive infections due to aspergillus and other filamentous Fungi","volume":"60","author":"Desai","year":"","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"3025","DOI":"10.1128\/aac.02942-15","article-title":"Population pharmacokinetics of Isavuconazole in subjects with mild or moderate hepatic impairment","volume":"60","author":"Desai","year":"","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref12","year":"2024"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1128\/cmr.12.4.501","article-title":"Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance","volume":"12","author":"Ghannoum","year":"1999","journal-title":"Clin. Microbiol. Rev."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e02032","DOI":"10.1128\/aac.02032-20","article-title":"A physiologically based pharmacokinetic analysis to predict the pharmacokinetics of intravenous isavuconazole in patients with or without hepatic impairment","volume":"65","author":"Huang","year":"2023","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1007\/s40262-023-01305-8","article-title":"Population pharmacokinetics of Total and unbound Isavuconazole in critically ill patients: implications for adaptive dosing strategies","volume":"62","author":"Jansen","year":"2023","journal-title":"Clin. Pharmacokinet."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.2147\/dddt.S145545","article-title":"Spotlight on isavuconazole in the treatment of invasive aspergillosis and mucormycosis: design, development, and place in therapy","volume":"12","author":"Jenks","year":"2018","journal-title":"Drug Des. Devel. Ther."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1007\/s40262-015-0236-8","article-title":"Reporting guidelines for clinical pharmacokinetic studies: the ClinPK statement","volume":"54","author":"Kanji","year":"2015","journal-title":"Clin. Pharmacokinet."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"4568","DOI":"10.1128\/aac.00514-16","article-title":"Isavuconazole population pharmacokinetic analysis using nonparametric estimation in patients with invasive fungal disease (results from the VITAL study)","volume":"60","author":"Kovanda","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e00101","DOI":"10.1128\/AAC.00101-17","article-title":"Impact of mucositis on absorption and systemic drug exposure of Isavuconazole","volume":"61","author":"Kovanda","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"e0017722","DOI":"10.1128\/aac.00177-22","article-title":"New perspectives on antimicrobial agents: isavuconazole","volume":"66","author":"Lewis","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1517\/17425255.2012.683859","article-title":"Evaluation of the pharmacokinetics and clinical utility of isavuconazole for treatment of invasive fungal infections","volume":"8","author":"Livermore","year":"2012","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/s0140-6736(15)01159-9","article-title":"Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial","volume":"387","author":"Maertens","year":"2016","journal-title":"Lancet"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"706","DOI":"10.3390\/antibiotics13080706","article-title":"Isavuconazole pharmacokinetics in critically ill patients: relationship with clinical effectiveness and patient safety","volume":"13","author":"Mart\u00edn-Cerezuela","year":"2024","journal-title":"Antibiotics (Basel)."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"115421","DOI":"10.1016\/j.addr.2024.115421","article-title":"Model-informed precision dosing: state of the art and future perspectives","volume":"215","author":"Minichmayr","year":"2024","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2020","journal-title":"BMJ"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"107157","DOI":"10.1016\/j.ejps.2025.107157","article-title":"Population pharmacokinetics of isavuconazole in hematologic patients: implications for model-informed precision dosing","volume":"212","author":"Pe\u00f1a-Lorenzo","year":"2025","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"211","DOI":"10.3390\/jof9020211","article-title":"Population pharmacokinetics of Isavuconazole in critical care patients with COVID-19-associated pulmonary aspergillosis and Monte Carlo simulations of high off-label doses","volume":"9","author":"Perez","year":"2023","journal-title":"J Fungi (Basel)."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"608","DOI":"10.3390\/jof9060608","article-title":"In vitro activity of isavuconazole and other mould-active azoles against Aspergillus fumigatus with and without CYP51 alterations","volume":"9","author":"Pfaller","year":"2023","journal-title":"J. Fungi"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1080\/17425255.2025.2545920","article-title":"Suboptimal concentrations of isavuconazole in critically ill patients treated for mold infections: a population pharmacokinetic analysis","volume":"21","author":"Rabault","year":"2025","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"143","DOI":"10.2147\/cpaa.S526869","article-title":"The effect of drug-drug interactions on the pharmacokinetics of isavuconazole: a comprehensive review","volume":"17","author":"Sang","year":"2025","journal-title":"Clin. Pharmacol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1586\/14787210.2015.990382","article-title":"Isavuconazole, a broad-spectrum triazole for the treatment of systemic fungal diseases","volume":"13","author":"Seyedmousavi","year":"2015","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1002\/jcph.2212","article-title":"Population pharmacokinetics, exposure-safety, and probability of target attainment analyses for Isavuconazole in Japanese patients with deep-seated mycoses","volume":"63","author":"Shirae","year":"2023","journal-title":"J. Clin. Pharmacol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1007\/s40265-016-0652-6","article-title":"Isavuconazole: a review in invasive aspergillosis and mucormycosis","volume":"76","author":"Shirley","year":"2016","journal-title":"Drugs"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"107619","DOI":"10.1016\/j.ijantimicag.2025.107619","article-title":"Therapeutic drug monitoring of isavuconazole: trends and update","volume":"66","author":"Tan","year":"2025","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1179\/joc.2009.21.3.272","article-title":"In vitro antifungal activity of isavuconazole against 345 mucorales isolates collected at study centers in eight countries","volume":"21","author":"Verweij","year":"2009","journal-title":"J. Chemother."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"e01728","DOI":"10.1128\/AAC.01728-19","article-title":"Population pharmacokinetics of intravenous Isavuconazole in solid-organ transplant recipients","volume":"64","author":"Wu","year":"2020","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"819","DOI":"10.3390\/pharmaceutics16060819","article-title":"Development and quality control of a population pharmacokinetic model library for Caspofungin","volume":"16","author":"Xu","year":"2024","journal-title":"Pharmaceutics."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1930025\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T05:21:28Z","timestamp":1791264088000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1930025\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":37,"alternative-id":["10.3389\/fmicb.2026.1930025"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1930025","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"1930025"}}