{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:05:54Z","timestamp":1788966354901,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:00:00Z","timestamp":1672876800000},"content-version":"vor","delay-in-days":44,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gilead Sciences through an Investigator Initiated Award","award":["IN-EU-131-D036"],"award-info":[{"award-number":["IN-EU-131-D036"]}]},{"DOI":"10.13039\/501100001713","name":"European Developing Countries Clinical Trials Partnership","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001713","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100004441","name":"Swedish International Development Cooperation Agency","doi-asserted-by":"crossref","award":["TRIA2015-1092"],"award-info":[{"award-number":["TRIA2015-1092"]}],"id":[{"id":"10.13039\/100004441","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Council"},{"name":"UKAID Joint Global Health Trials","award":["MR\/P006922\/1"],"award-info":[{"award-number":["MR\/P006922\/1"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Global Health Research Professorship","award":["RP-2017-08-ST2-012"],"award-info":[{"award-number":["RP-2017-08-ST2-012"]}]},{"name":"MRC\/DFID African Research Leader","award":["MR\/P020526\/1"],"award-info":[{"award-number":["MR\/P020526\/1"]}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["203919\/Z\/16\/Z"],"award-info":[{"award-number":["203919\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Single, high-dose liposomal amphotericin B (LAmB; AmBisome, Gilead Sciences) has demonstrated non-inferiority to amphotericin B deoxycholate in combination with other antifungals for averting all-cause mortality from HIV-associated cryptococcal meningitis. There are limited data on the pharmacokinetics (PK) of AmBisome. The aim of this study was to describe population PK of AmBisome and conduct a meta-analysis of the available studies to suggest the optimal dosing for cryptococcal meningoencephalitis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data from a Phase II and Phase III trial of high-dose, short-course AmBisome for cryptococcal meningoencephalitis were combined to develop a population PK model. A search was conducted for trials of AmBisome monotherapy and meta-analysis of clinical outcome data was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A two-compartment model with first-order clearance of drug from the central compartment fitted the data best and enabled the extent of inter-individual variability in PK to be quantified. Mean (SD) population PK parameter estimates were: clearance 0.416 (0.363) \u2005L\/h; volume of distribution 4.566 (4.518)\u2005L; first-order transfer of drug from central to peripheral compartments 2.222 (3.351) \u2005h\u22121, and from peripheral to central compartment 2.951 (4.070) \u2005h\u22121. Data for the meta-analysis were insufficient to suggest optimal dosing of AmBisome for cryptococcal meningoencephalitis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study provides novel insight into the PK of AmBisome at the population level and the variability therein. Our analysis also serves to highlight the paucity of data available on the pharmacodynamics (PD) of AmBisome and underscores the importance of thorough and detailed PK\/PD analysis in the development of novel antifungals, by demonstrating the challenges associated with post hoc PK\/PD analysis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkac389","type":"journal-article","created":{"date-parts":[[2022,11,22]],"date-time":"2022-11-22T03:35:46Z","timestamp":1669088146000},"page":"276-283","source":"Crossref","is-referenced-by-count":8,"title":["Population pharmacokinetics of liposomal amphotericin B in adults with HIV-associated cryptococcal meningoencephalitis"],"prefix":"10.1093","volume":"78","author":[{"given":"Katharine E","family":"Stott","sequence":"first","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology, University of Liverpool , UK"},{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Moyo","sequence":"additional","affiliation":[{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"},{"name":"Department of Medicine, Kamuzu University of Health Sciences , Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajisa","family":"Ahmadu","sequence":"additional","affiliation":[{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheusisime","family":"Kajanga","sequence":"additional","affiliation":[{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebbie","family":"Gondwe","sequence":"additional","affiliation":[{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wezzie","family":"Chimang\u2019anga","sequence":"additional","affiliation":[{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalitso","family":"Chasweka","sequence":"additional","affiliation":[{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tshepo B","family":"Leeme","sequence":"additional","affiliation":[{"name":"Botswana-University of Pennsylvania Partnership , Gaborone, Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mooketsi","family":"Molefi","sequence":"additional","affiliation":[{"name":"University of Botswana , Gaborone, Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awilly","family":"Chofle","sequence":"additional","affiliation":[{"name":"National Institute of Medical Research , Mwanza , Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Bidwell","sequence":"additional","affiliation":[{"name":"National Institute of Medical Research , Mwanza , Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Changalucha","sequence":"additional","affiliation":[{"name":"National Institute of Medical Research , Mwanza , Tanzania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Unsworth","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology, University of Liverpool , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Jimenez-Valverde","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology, University of Liverpool , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine , London , UK"},{"name":"Botswana Harvard AIDS Institute Partnership , Gaborone , Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry C","family":"Mwandumba","sequence":"additional","affiliation":[{"name":"Malawi Liverpool Wellcome Programme, Kamuzu University of Health Sciences , Malawi"},{"name":"Department of Medicine, Kamuzu University of Health Sciences , Malawi"},{"name":"Department of Clinical Sciences, Liverpool School of Tropical 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Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology, University of Liverpool , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6478-1959","authenticated-orcid":false,"given":"Anne-Grete","family":"M\u00e4rtson","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics, Department of Pharmacology, University of Liverpool , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,22]]},"reference":[{"key":"2023010801151382400_dkac389-B1","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1056\/NEJMoa2111904","article-title":"Single-dose liposomal amphotericin B treatment for cryptococcal meningitis","volume":"386","author":"Jarvis","year":"2022","journal-title":"N 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