{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T04:16:11Z","timestamp":1791260171664,"version":"4.1.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To study the population pharmacokinetics of micafungin in critically ill patients, evaluate and optimize dosage regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>An HPLC\u2013fluorescence bioassay for micafungin was developed, fully validated and applied to a pharmacokinetic study conducted in 14 ICU patients. Dense blood sampling was performed from days 1 to 7. A population pharmacokinetic model accounting for interindividual (IIV) and interoccasion variability (IOV) of the PK parameters was developed. Simulations were performed to estimate the probability of target attainment (PTA) for several dosing regimens.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Key findings<\/jats:title>\n                  <jats:p>A two-compartment pharmacokinetic model best described the data, with population clearance CL = 1.31 L\/h and central volume V1 = 14.2 L. The relatively high IOV observed (45% for CL, 27% for V1) sets limits for the dose individualization in this population. The low PTA on the first day of treatment suggests the need of a loading dose. PTA and CFR estimates show that the current micafungin dosage may be insufficient for the treatment of borderline susceptible Candida strains.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A loading dose of up to 300 mg of micafungin is needed for the treatment of invasive candidiasis in ICU patients while a maintenance dose of up to 200 mg can be considered in empirical antifungal treatment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1111\/jphp.13353","type":"journal-article","created":{"date-parts":[[2020,8,13]],"date-time":"2020-08-13T06:45:25Z","timestamp":1597301125000},"page":"1750-1760","source":"Crossref","is-referenced-by-count":13,"title":["Population pharmacokinetics of micafungin over repeated doses in critically ill patients: a need for a loading dose?"],"prefix":"10.1093","volume":"72","author":[{"given":"Iasonas","family":"Kapralos","sequence":"first","affiliation":[{"name":"Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, National and Kapodistrian University of Athens , Athens,","place":["Greece"]},{"name":"Pharma-Informatics Unit, Athena Research and Innovation Center in Information Communication and Knowledge Technologies , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstratios","family":"Mainas","sequence":"additional","affiliation":[{"name":"Intensive Care Unit, Hippokration General Hospital of Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efthymios","family":"Neroutsos","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, National and Kapodistrian University of Athens , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella","family":"Apostolidi","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, National and Kapodistrian University of Athens , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-1007","authenticated-orcid":false,"given":"Maria","family":"Siopi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olympia","family":"Apostolopoulou","sequence":"additional","affiliation":[{"name":"Department of Clinical Care Medicine, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Dimopoulos","sequence":"additional","affiliation":[{"name":"Department of Clinical Care Medicine, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Sambatakou","sequence":"additional","affiliation":[{"name":"2nd Department of Internal Medicine, Hippokration General Hospital , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgia","family":"Valsami","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, National and Kapodistrian University of Athens , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8869-1509","authenticated-orcid":false,"given":"Joseph","family":"Meletiadis","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University General Hospital, Medical School, National and Kapodistrian University of Athens , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5087-4003","authenticated-orcid":false,"given":"Aristides","family":"Dokoumetzidis","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics-Pharmacokinetics, Department of Pharmacy, National and Kapodistrian University of Athens , Athens,","place":["Greece"]},{"name":"Pharma-Informatics Unit, Athena Research and Innovation Center in Information Communication and Knowledge Technologies , Athens,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"2024110604202443000_jphp13353-cit-0001","first-page":"1","article-title":"Invasive candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat Rev Dis Prim"},{"key":"2024110604202443000_jphp13353-cit-0002","volume-title":"Mycamine (micafungin), Highlights of prescribing information","author":"Astellas Pharmaceuticals USA","year":"2013"},{"key":"2024110604202443000_jphp13353-cit-0003","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1086\/501020","article-title":"Micafungin: a new echinocandin","volume":"42","author":"Chandrasekar","year":"2006","journal-title":"Clin Infect Dis"},{"key":"2024110604202443000_jphp13353-cit-0004","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1177\/0091270005279580","article-title":"Pharmacokinetics of micafungin in healthy volunteers, volunteers with moderate liver disease, and volunteers with renal dysfunction","volume":"45","author":"Hebert","year":"2005","journal-title":"J Clin Pharmacol"},{"key":"2024110604202443000_jphp13353-cit-0005","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/s13318-014-0204-y","article-title":"Pharmacokinetics of micafungin in subjects with severe hepatic dysfunction","volume":"40","author":"Undre","year":"2015","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"2024110604202443000_jphp13353-cit-0006","doi-asserted-by":"crossref","first-page":"4403","DOI":"10.1128\/AAC.00623-15","article-title":"Altered micafungin pharmacokinetics in intensive care unit patients","volume":"59","author":"Lempers","year":"2015","journal-title":"Antimicrob Agents Chemother"},{"key":"2024110604202443000_jphp13353-cit-0007","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1007\/s40262-017-0509-5","article-title":"Population pharmacokinetic model and pharmacokinetic target attainment of micafungin in intensive care unit patients","volume":"56","author":"Martial","year":"2017","journal-title":"Clin Pharmacokinet"},{"key":"2024110604202443000_jphp13353-cit-0008","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1093\/jac\/dkw352","article-title":"Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation","volume":"72","author":"Jullien","year":"2017","journal-title":"J Antimicrob Chemother"},{"key":"2024110604202443000_jphp13353-cit-0009","doi-asserted-by":"crossref","first-page":"5914","DOI":"10.1128\/AAC.00727-16","article-title":"Comparative population plasma and tissue pharmacokinetics of micafungin in critically ill patients with severe burn injuries and patients with complicated intra-abdominal infection","volume":"60","author":"Garc\u00eda-De-Lorenzo","year":"2016","journal-title":"Antimicrob Agents 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