{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T20:43:14Z","timestamp":1771015394356,"version":"3.50.1"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2010,8,1]],"date-time":"2010-08-01T00:00:00Z","timestamp":1280620800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Invasive pulmonary aspergillosis is a life-threatening infection in lung transplant recipients; however, no studies of the pharmacokinetics and pharmacodynamics (PKPD) of echinocandins in transplanted lungs have been reported. We conducted a single-dose prospective study of the intrapulmonary and plasma PKPD of 150 mg of micafungin administered intravenously in 20 adult lung transplant recipients. Epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage performed 3, 5, 8, 18, or 24 h after initiation of infusion. Micafungin concentrations in plasma, ELF, and ACs were determined using high-pressure liquid chromatography. Noncompartmental methods, population analysis, and multiple-dose simulations were used to calculate PKPD parameters.<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>in plasma, ELF, and ACs was 4.93, 1.38, and 17.41 \u03bcg\/ml, respectively. The elimination half-life in plasma was 12.1 h. Elevated concentrations in ELF and ACs were sustained during the 24-h sampling period, indicating prolonged compartmental half-lives. The mean micafungin concentration exceeded the MIC<jats:sub>90<\/jats:sub>of<jats:italic>A<\/jats:italic><jats:italic>spergillus<\/jats:italic><jats:italic>fumigatus<\/jats:italic>(0.0156 \u03bcg\/ml) in plasma (total and free), ELF, and ACs throughout the dosing interval. The area under the time-concentration curve from 0 to 24 h (AUC<jats:sub>0-24<\/jats:sub>)\/MIC<jats:sub>90<\/jats:sub>ratios in plasma, ELF, and ACs were 5,077, 923.1, and 13,340, respectively. Multiple-dose simulations demonstrated that ELF and AC concentrations of micafungin would continue to increase during 14 days of administration. We conclude that a single 150-mg intravenous dose of micafungin resulted in plasma, ELF, and AC concentrations that exceeded the MIC<jats:sub>90<\/jats:sub>of<jats:italic>A. fumigatus<\/jats:italic>for 24 h and that these concentrations would continue to increase during 14 days of administration, supporting its potential activity for prevention and early treatment of pulmonary aspergillosis.<\/jats:p>","DOI":"10.1128\/aac.01647-09","type":"journal-article","created":{"date-parts":[[2010,5,4]],"date-time":"2010-05-04T01:57:40Z","timestamp":1272938260000},"page":"3451-3459","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":36,"title":["Intrapulmonary Pharmacokinetics and Pharmacodynamics of Micafungin in Adult Lung Transplant Patients"],"prefix":"10.1128","volume":"54","author":[{"given":"Thomas J.","family":"Walsh","sequence":"first","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sylvain","family":"Goutelle","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon, Ho\u0302pital A. 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