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Serial blood samples were collected over a single-dosing interval during ECMO. Total plasma concentrations were measured by a validated chromatographic assay. A population pharmacokinetic model was built and Monte Carlo dosing simulations were performed using Monolix. The probability of target attainment (PTA) and fractional target attainment (FTA) rates were simulated for various caspofungin dosing regimens against\n              <jats:italic>Candida albicans<\/jats:italic>\n              ,\n              <jats:italic>Candida glabrata<\/jats:italic>\n              , and\n              <jats:italic>Candida parapsilosis<\/jats:italic>\n              . In all, 64 plasma concentration-time points were obtained from 8 critically ill patients receiving ECMO. Plasma concentration-time data for caspofungin were best described by a one-compartment model with first-order elimination. Lean body weight was identified as a significant covariate of volume of distribution. The typical volume of distribution and clearance of caspofungin in this cohort were 8.13 L and 0.55 L\/h, respectively. The licensed caspofungin dosing regimen (a loading dose of 70 mg on day 1 followed by a maintenance dose of either 50 mg\/day or 70 mg\/day) demonstrated optimal PTA rates (\u226590%) against\n              <jats:italic>C. albicans<\/jats:italic>\n              with an MIC of \u22640.064 mg\/L,\n              <jats:italic>C. glabrata<\/jats:italic>\n              with an MIC of \u22640.125 mg\/L, and\n              <jats:italic>C. parapsilosis<\/jats:italic>\n              with an MIC of \u22640.064 mg\/L. The FTA analysis suggested that the licensed dosing regimen is only optimal (\u226595%) against\n              <jats:italic>Candida glabrata<\/jats:italic>\n              , regardless of lean body weight. A higher-than-standard empirical dosing regimen (e.g., a loading dose of 100 mg on day 1, followed by a maintenance dose of 100 mg daily) is likely advantageous for critically ill patients receiving ECMO.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01435-24","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T14:00:42Z","timestamp":1734530442000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Population pharmacokinetics of caspofungin in critically ill patients receiving extracorporeal membrane oxygenation\u2014an ASAP ECMO study"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8889-5579","authenticated-orcid":true,"given":"Mohd H.","family":"Abdul-Aziz","sequence":"first","affiliation":[{"name":"University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of 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Faculty of Medicine, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Corley","sequence":"additional","affiliation":[{"name":"Critical Care Research Group and Adult Intensive Care Services, The Prince Charles Hospital","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Gilder","sequence":"additional","affiliation":[{"name":"Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital","place":["Auckland, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Levkovich","sequence":"additional","affiliation":[{"name":"Experiential Development and Graduate Education and Centre for Medicines Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University","place":["Melbourne, 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Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Department of Intensive Care and Hyperbaric Medicine, The Alfred Hospital","place":["Melbourne, Australia"]},{"name":"School of Public Health and Preventive Medicine, Monash University","place":["Melbourne, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven C.","family":"Wallis","sequence":"additional","affiliation":[{"name":"University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland","place":["Brisbane, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Fraser","sequence":"additional","affiliation":[{"name":"Critical Care Research Group and Adult Intensive Care Services, The Prince Charles Hospital","place":["Brisbane, Australia"]},{"name":"Faculty of Medicine, The University of 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