{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:47:09Z","timestamp":1784692029986,"version":"3.55.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T00:00:00Z","timestamp":1503532800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100000265","name":"RCUK | Medical Research Council","doi-asserted-by":"publisher","award":["MR\/J008702\/1"],"award-info":[{"award-number":["MR\/J008702\/1"]}],"id":[{"id":"10.13039\/501100000265","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":[[2017,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Visceral leishmaniasis is a neglected tropical disease that causes significant morbidity and mortality worldwide. Characterization of the pharmacokinetics and pharmacodynamics of antileishmanial drugs in preclinical models is important for drug development and use. Here we investigated the pharmacodynamics and drug distribution of liposomal amphotericin B (AmBisome) in\n            <jats:named-content content-type=\"genus-species\">Leishmania donovani<\/jats:named-content>\n            -infected BALB\/c mice at three different dose levels and two different time points after infection. We additionally compared drug levels in plasma, liver, and spleen in infected and uninfected BALB\/c mice over time. At the highest administered dose of 10 mg\/kg AmBisome, &gt;90% parasite inhibition was observed within 2 days after drug administration, consistent with drug distribution from blood to tissue within 24 h and a fast rate of kill. Decreased drug potency was observed in the spleen when AmBisome was administered on day 35 after infection, compared to day 14 after infection. Amphotericin B concentrations and total drug amounts per organ were lower in liver and spleen when AmBisome was administered at the advanced stage of infection and compared to those in uninfected BALB\/c mice. However, the magnitude of difference was lower when total drug amounts per organ were estimated. Differences were also noted in drug distribution to\n            <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n            -infected livers and spleens. Taken together, our data suggest that organ enlargement and other pathophysiological factors cause infection- and organ-specific drug distribution and elimination after administration of single-dose AmBisome to\n            <jats:named-content content-type=\"genus-species\">L. donovani<\/jats:named-content>\n            -infected mice. Plasma drug levels were not reflective of changes in drug levels in tissues.\n          <\/jats:p>","DOI":"10.1128\/aac.00497-17","type":"journal-article","created":{"date-parts":[[2017,6,20]],"date-time":"2017-06-20T00:30:28Z","timestamp":1497918628000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":25,"title":["Pharmacodynamics and Biodistribution of Single-Dose Liposomal Amphotericin B at Different Stages of Experimental Visceral Leishmaniasis"],"prefix":"10.1128","volume":"61","author":[{"given":"Andrew A.","family":"Voak","sequence":"first","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene &amp; Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Harris","sequence":"additional","affiliation":[{"name":"Pharmidex, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshan","family":"Qaiser","sequence":"additional","affiliation":[{"name":"Pharmidex, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon L.","family":"Croft","sequence":"additional","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene &amp; Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Seifert","sequence":"additional","affiliation":[{"name":"Faculty of Infectious and Tropical Diseases, Department of Immunology and Infection, London School of Hygiene &amp; Tropical Medicine, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035671"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1517\/14728214.2012.748036"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004304"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0903627"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(13)70118-9"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62050-8"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/49.suppl_1.21"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-013-1127-z"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp465"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.10.2722"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.2005.25.12part2.150S"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-13"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/639304"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2004.08.009"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2015.35"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2613.2001.00199.x"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00035"},{"key":"e_1_3_3_19_2","unstructured":"Salguero\nFJ Garcia-JimenezWL LimaI SeifertK. 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