{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:18:46Z","timestamp":1778753926578,"version":"3.51.4"},"reference-count":27,"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>\n          <jats:p>\n            The pharmacodynamic and pharmacokinetic (PK-PD) properties of amphotericin B (AmB) formulations against invasive pulmonary aspergillosis (IPA) are not well understood. We used an\n            <jats:italic>in vitro<\/jats:italic>\n            model of IPA to further elucidate the PK-PD of amphotericin B deoxycholate (DAmB), liposomal amphotericin B (LAmB) and amphotericin B lipid complex (ABLC). The pharmacokinetics of these formulations for endovascular fluid, endothelial cells, and alveolar cells were estimated. Pharmacodynamic relationships were defined by measuring concentrations of galactomannan in endovascular and alveolar compartments. Confocal microscopy was used to visualize fungal biomass. A mathematical model was used to calculate the area under the concentration-time curve (AUC) in each compartment and estimate the extent of drug penetration. The interaction of LAmB with host cells and hyphae was visualized using sulforhodamine B-labeled liposomes. The MICs for the pure compound and the three formulations were comparable (0.125 to 0.25 mg\/liter). For all formulations, concentrations of AmB progressively declined in the endovascular fluid as the drug distributed into the cellular bilayer. Depending on the formulation, the AUCs for AmB were 10 to 300 times higher within the cells than within endovascular fluid. The concentrations producing a 50% maximal effect (EC\n            <jats:sub>50<\/jats:sub>\n            ) in the endovascular compartment were 0.12, 1.03, and 4.41 mg\/liter for DAmB, LAmB, and ABLC, respectively, whereas, the EC\n            <jats:sub>50<\/jats:sub>\n            in the alveolar compartment were 0.17, 7.76, and 39.34 mg\/liter, respectively. Confocal microscopy suggested that liposomes interacted directly with hyphae and host cells. The PK-PD relationships of the three most widely used formulations of AmB differ markedly within an\n            <jats:italic>in vitro<\/jats:italic>\n            lung model of IPA.\n          <\/jats:p>","DOI":"10.1128\/aac.01586-09","type":"journal-article","created":{"date-parts":[[2010,5,4]],"date-time":"2010-05-04T01:57:40Z","timestamp":1272938260000},"page":"3432-3441","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Pharmacokinetics and Pharmacodynamics of Amphotericin B Deoxycholate, Liposomal Amphotericin B, and Amphotericin B Lipid Complex in an\n            <i>In Vitro<\/i>\n            Model of Invasive Pulmonary Aspergillosis"],"prefix":"10.1128","volume":"54","author":[{"given":"Jodi M.","family":"Lestner","sequence":"first","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan J.","family":"Howard","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Goodwin","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lea","family":"Gregson","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayesh","family":"Majithiya","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerard M.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Gilead Sciences, San Dimas, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"The University of Manchester, Manchester Academic Health Science Centre, NIHR Translational Research Facility in Respiratory Medicine, University Hospital of South Manchester NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2008.01979.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.2.674-684.2006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/319211"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.3.834-840.2002"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.3.7663787"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.1.140-146.2002"},{"key":"e_1_3_2_8_2","unstructured":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi. 2002"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/514341"},{"key":"e_1_3_2_10_2","unstructured":"D'Argenio D. Z. and A. Schumitzky. 1997. ADAPT II. A program for simulation identification and optimal experimental design. User manual. Biomedical Simulations Resource University of Southern California Los Angeles CA. http:\/\/bmsr.esc.edu\/\n."},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.2005.25.12part2.150S"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00241-06"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1080\/13693780802510232"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02913.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00601-06"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1086\/510535"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1080\/107175499266995"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00662-08"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.12.2.310"},{"key":"e_1_3_2_20_2","first-page":"389","year":"2001","unstructured":"Leary, R., R. Jelliffe, A. Schumitzky, and M. van Guilder. 2001. An adaptive grid, non-parametric approach to pharmacokinetic and dynamic (PK\/PD) models, p. 389-394. In Proceedings of the 14th IEEE Symposium on Computer-Based Medical Systems. IEEE Computer Society, Bethesda, MD.","journal-title":"IEEE Computer Society, Bethesda, MD"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01268-06"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1159\/000239202"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1086\/592255"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/596757"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/525258"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903113401004"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3487-3496.2001"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1086\/313498"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01586-09","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01586-09","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:24:12Z","timestamp":1645475052000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01586-09"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,8]]},"references-count":27,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["10.1128\/AAC.01586-09"],"URL":"https:\/\/doi.org\/10.1128\/aac.01586-09","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,8]]},"assertion":[{"value":"2009-11-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-04-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2010-08-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}