{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:54:55Z","timestamp":1793829295126,"version":"4.6.1"},"reference-count":24,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2006,2,1]],"date-time":"2006-02-01T00:00:00Z","timestamp":1138752000000},"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":[[2006,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We conducted a dose fractionation study of neutropenic, corticosteroid-immunosuppressed mice to characterize the pharmacodynamic\/pharmacokinetic (PK\/PD) parameter most closely associated with amphotericin B (AMB) efficacy in the treatment of invasive pulmonary aspergillosis. Pharmacokinetic parameter estimates were determined by a nonparametric population pharmacokinetic analysis of plasma drug concentrations following single intraperitoneal doses (0.25, 1.0, and 3.0 mg\/kg of body weight) of amphotericin B deoxycholate. Three dosage groups (0.5, 0.75, and 1.0 mg\/kg) fractionated into three dosing intervals (every 8 h [q8h], q24h, or q72h) were tested to discriminate between the PK\/PD parameters (the ratio of maximum concentration of drug in serum [\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ]\/MIC, the ratio of area under the concentration-time curve\/MIC, and percentage of time above MIC) most closely associated with AMB efficacy over a range of clinically achievable exposures in humans. The efficacy of each regimen was determined by quantitative PCR and survival. Reductions in pulmonary fungal burden and improvements in survival were maximized at the highest peak plasma concentrations in each of the dosage groups. Reductions in pulmonary fungal burden and increased survival were most closely associated with\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            \/MIC, with maximal activity occurring as the\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            \/MIC approached 2.4. In our model,\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            \/MIC is the PK\/PD parameter most closely associated with efficacy in the treatment of invasive pulmonary aspergillosis. These data predict that less frequently administered, higher dosages of AMB would optimize efficacy.\n          <\/jats:p>","DOI":"10.1128\/aac.50.2.469-473.2006","type":"journal-article","created":{"date-parts":[[2006,1,25]],"date-time":"2006-01-25T21:53:41Z","timestamp":1138226021000},"page":"469-473","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":90,"title":["Pharmacodynamic Activity of Amphotericin B Deoxycholate Is Associated with Peak Plasma Concentrations in a Neutropenic Murine Model of Invasive Pulmonary Aspergillosis"],"prefix":"10.1128","volume":"50","author":[{"given":"Nathan P.","family":"Wiederhold","sequence":"first","affiliation":[{"name":"The University of Texas at Austin College of Pharmacy, Austin"},{"name":"The University of Texas Health Science Center at San Antonio, San Antonio, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent H.","family":"Tam","sequence":"additional","affiliation":[{"name":"The University of Houston College of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingduan","family":"Chi","sequence":"additional","affiliation":[{"name":"The University of Houston College of Pharmacy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall A.","family":"Prince","sequence":"additional","affiliation":[{"name":"The University of Houston College of Pharmacy"},{"name":"The University of Texas M. D. Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios P.","family":"Kontoyiannis","sequence":"additional","affiliation":[{"name":"The University of Houston College of Pharmacy"},{"name":"The University of Texas M. D. Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"The University of Houston College of Pharmacy"},{"name":"The University of Texas M. D. Anderson Cancer Center, Houston"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001432-200412000-00005"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.4.1179-1186.2003"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.3.922-926.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/319985"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.3.834-840.2002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3474-3481.2001"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/152.5.1037"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.3.362"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.57.5.1452-1456.1989"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.26.4.446"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.6.1392"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-002-0699-z"},{"key":"e_1_3_2_14_2","unstructured":"Leary R. R. Jelliffe A. Schumitzky and M. Van Guilder. 2001. Presented at the 14th IEEE Symposium on Computer-Based Medical Systems Bethesda Md. 26 to 27 July."},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1382"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.10.3208-3214.2002"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.3.945-951.2005"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1086\/339202"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.758-764.2004"},{"key":"e_1_3_2_20_2","unstructured":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi 2002 vol. 22"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/37.3.465"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1086\/376634"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.4.1642-1645.2005"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1086\/424465"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1086\/514704"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.50.2.469-473.2006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.50.2.469-473.2006","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T18:58:59Z","timestamp":1645469939000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.50.2.469-473.2006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,2]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2006,2]]}},"alternative-id":["10.1128\/AAC.50.2.469-473.2006"],"URL":"https:\/\/doi.org\/10.1128\/aac.50.2.469-473.2006","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,2]]},"assertion":[{"value":"2005-07-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}