{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T02:27:07Z","timestamp":1790821627633,"version":"4.1.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100014471","name":"Mundipharma Research Limited","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014471","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010643","name":"Cidara Therapeutics","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010643","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2023,12,14]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Rezafungin is a chemically and metabolically stable echinocandin with a longer half-life than other echinocandins, allowing for a once-weekly intravenous infusion versus a daily infusion. Rezafungin is approved in the US for the treatment of candidemia and\/or invasive candidiasis and is in development for the prevention of invasive fungal disease caused by\n            <jats:italic>Candida<\/jats:italic>\n            ,\n            <jats:italic>Aspergillus<\/jats:italic>\n            , and\n            <jats:italic>Pneumocystis<\/jats:italic>\n            spp. in immunosuppressed patients. A population pharmacokinetic (PPK) model was developed using data from five Phase 1, one Phase 2, and one Phase 3 study. The model found to best describe the available data was a three-compartment PPK model with first-order elimination characterized by the parameters clearance (CL), central volume (V1), peripheral volume (V23), intercompartmental clearance 1, and intercompartmental clearance 2. The variability model included correlated interindividual variability in CL, V1, and V23 and a proportional residual variability model. The following statistically significant covariates were identified: albumin concentrations on V23; body surface area (BSA) on CL, V1, and V23; and disease state on CL and V1. Disease states were defined as patients from the Phase 2 and Phase 3 studies and hepatically impaired subjects. Covariates of BSA, disease state, or albumin, included in the final model, were not associated with clinically meaningful changes in PK, nor were any other patient factors, indicating that a common dose regimen is adequate for all adult patients. Target attainment simulations were performed to estimate the probability of achieving PK\/pharmacodynamic targets across the range of minimum inhibitory concentration values for six species of\n            <jats:italic>Candida<\/jats:italic>\n            .\n          <\/jats:p>","DOI":"10.1128\/aac.00916-23","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T14:01:00Z","timestamp":1701180060000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["Population pharmacokinetic modeling and target attainment analyses of rezafungin for the treatment of candidemia and invasive candidiasis"],"prefix":"10.1128","volume":"67","author":[{"given":"Stefan","family":"Roepcke","sequence":"first","affiliation":[{"name":"Cognigen Division of Simulations Plus, Inc., Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2034-6274","authenticated-orcid":false,"given":"Julie","family":"Passarell","sequence":"additional","affiliation":[{"name":"Cognigen Division of Simulations Plus, Inc., Buffalo, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1891-2012","authenticated-orcid":false,"given":"Helen","family":"Walker","sequence":"additional","affiliation":[{"name":"Mundipharma, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0464-9301","authenticated-orcid":false,"given":"Shawn","family":"Flanagan","sequence":"additional","affiliation":[{"name":"Cidara Therapeutics, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01430-10"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky013"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofac492.644"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00621-11"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkv173"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02565-20"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofy358"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa502"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2019.03.028"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02603-17"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00842-21"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa1380"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)02324-8"},{"key":"e_1_3_2_18_2","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts","author":"Clinical and Laboratory Standards Institute","year":"2017","unstructured":"Clinical and Laboratory Standards Institute. 2017. Reference method for broth dilution antifungal susceptibility testing of yeasts. 4th ed. Clinical and Laboratory Standards Institute standard M27, Wayne, PA.","edition":"4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02614-17"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw214"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12640"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2017.07.007"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2017.03.028"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkx008"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02045-16"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2017.10.021"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkz390"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00099-20"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.02449-21"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00566-08"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01584-09"},{"key":"e_1_3_2_32_2","volume-title":"NONMEM 7.3.0 users guides (1989-2013)","author":"Beal SL","unstructured":"Beal SL, Sheiner LB, Boeckmann AJ, Bauer RJ, eds. NONMEM 7.3.0 users guides (1989-2013). ICON Development Solutions, Hanover, MD."},{"key":"e_1_3_2_33_2","volume-title":"Clinical guide to laboratory data","author":"Tietz NW","year":"2006","unstructured":"Tietz NW, Wu AHB. 2006. Clinical guide to laboratory data. 4th ed. Saunders Elsevier, St. Louis, MO.","edition":"4"},{"key":"e_1_3_2_34_2","unstructured":"Baron K. mrgsolve: simulate from ODE-based models. 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