{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T23:50:34Z","timestamp":1788306634399,"version":"build-2803163510"},"reference-count":18,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2016,12,1]],"date-time":"2016-12-01T00:00:00Z","timestamp":1480550400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100004948","name":"Astellas Pharma","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004948","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Liposomal amphotericin B (LAmB) is widely used in the treatment of invasive fungal disease (IFD) in adults and children. There are relatively limited pharmacokinetic (PK) data to inform optimal dosing in children that achieves systemic drug exposures comparable to those of adults. Our objective was to describe the pharmacokinetics of LAmB in children aged 1 to 17 years with suspected or documented IFD. Thirty-five children were treated with LAmB at doses of 2.5 to 10 mg kg\n            <jats:sup>\u22121<\/jats:sup>\n            daily. Samples were taken at baseline and at 0.5- to 2.0-h intervals for 24 h after receipt of the first dose (\n            <jats:italic>n<\/jats:italic>\n            = 35 patients) and on the final day of therapy (\n            <jats:italic>n<\/jats:italic>\n            = 25 patients). LAmB was measured using high-performance liquid chromatography (HPLC). The relationship between drug exposure and development of toxicity was explored. An evolution in PK was observed during the course of therapy, resulting in a proportion of patients (\n            <jats:italic>n<\/jats:italic>\n            = 13) having significantly higher maximum serum concentrations (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>max<\/jats:sub>\n            ) and areas under the concentration-time curve from 0 to 24 h (AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            ) later in the course of therapy, without evidence of drug accumulation (trough plasma concentration accumulation ratio of &lt;1.2). The fit of a 2-compartment model incorporating weight and an exponential decay function describing volume of distribution best described the data. There was a statistically significant relationship between mean AUC\n            <jats:sub>0\u201324<\/jats:sub>\n            and probability of nephrotoxicity (odds ratio, 2.37; 95% confidence interval, 1.84 to 3.22;\n            <jats:italic>P<\/jats:italic>\n            = 0.004). LAmB exhibits nonlinear pharmacokinetics. A third of children appear to experience a time-dependent change in PK, which is not explained by weight, maturation, or observed clinical factors.\n          <\/jats:p>","DOI":"10.1128\/aac.01427-16","type":"journal-article","created":{"date-parts":[[2016,10,4]],"date-time":"2016-10-04T02:59:06Z","timestamp":1475549946000},"page":"7340-7346","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Population Pharmacokinetics of Liposomal Amphotericin B in Immunocompromised Children"],"prefix":"10.1128","volume":"60","author":[{"given":"Jodi M.","family":"Lestner","sequence":"first","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Groll","sequence":"additional","affiliation":[{"name":"Center for Bone Marrow Transplantation and Department of Pediatric Hematology\/Oncology, University Children's Hospital M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghaith","family":"Aljayyoussi","sequence":"additional","affiliation":[{"name":"Liverpool School of Tropical Medicine, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nita L.","family":"Seibel","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"},{"name":"Children's National Medical Center and George Washington University School of Medicine and Public Health, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aziza","family":"Shad","sequence":"additional","affiliation":[{"name":"Clinical Investigations Branch, Cancer Treatment Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corina","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Hematology\/Oncology, Georgetown University Medical Center, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren V.","family":"Wood","sequence":"additional","affiliation":[{"name":"Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul F.","family":"Jarosinski","sequence":"additional","affiliation":[{"name":"Pharmacy Department, National Institutes of Health Clinical Center, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA"},{"name":"Transplantation-Oncology Infectious Disease Program, Weill Cornell Medical Center, New York, New York, USA"},{"name":"Department of Pediatrics, Weill Cornell Medical Center, New York, New York, USA"},{"name":"Department of Microbiology, Weill Cornell Medical Center, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/514341"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/515033"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.12.3487-3496.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3109\/13693780903311944"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.3.935-942.2006"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00933-12"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00265-11"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199610000-00014"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31825c4ba6"},{"key":"e_1_3_2_11_2","volume-title":"ADAPT 5 user's guide: pharmacokinetic\/pharmacodynamic systems analysis software","author":"D'Argenio DZ","year":"2009","unstructured":"D'Argenio DZ, Schumitzky A, Wang X. 2009. ADAPT 5 user's guide: pharmacokinetic\/pharmacodynamic systems analysis software. Biomedical Simulations Resource, Los Angeles, CA."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/653606"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12040"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/525258"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199903113401004"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.9.2224"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.12.3146"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600830716"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.2.223"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01427-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.01427-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T20:27:01Z","timestamp":1645475221000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.01427-16"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,12]]},"references-count":18,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1128\/AAC.01427-16"],"URL":"https:\/\/doi.org\/10.1128\/aac.01427-16","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,12]]},"assertion":[{"value":"2016-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-11-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}