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A PK study was conducted in<jats:italic>n<\/jats:italic>= 42 patients receiving DAmB (1 mg\/kg of body weight every 24 h [q24h]). A 2-compartment PK model was developed. Patient weight influenced clearance and volume in the final structural model. Monte Carlo simulations estimated drug exposure associated with various DAmB dosages. A search was conducted for trials reporting outcomes of treatment of cryptococcal meningitis patients with DAmB monotherapy, and a meta-analysis was performed. The PK parameter means (standard deviations) were as follows: clearance, 0.03 (0.01) \u00d7 weight + 0.67 (0.01) liters\/h; volume, 0.82 (0.80) \u00d7 weight + 1.76 (1.29) liters; first-order rate constant from central compartment to peripheral compartment, 5.36 (6.67) h<jats:sup>\u22121<\/jats:sup>; first-order rate constant from peripheral compartment to central compartment, 9.92 (12.27) h<jats:sup>\u22121<\/jats:sup>. The meta-analysis suggested that the DAmB dosage explained most of the heterogeneity in cerebrospinal fluid (CSF) sterility outcomes but not in mortality outcomes. Simulations of values corresponding to the area under concentration-time curve from h 144 to h 168 (AUC<jats:sub>144\u2013168<\/jats:sub>) resulted in median (interquartile range) values of 5.83 mg \u00b7 h\/liter (4.66 to 8.55), 10.16 mg \u00b7 h\/liter (8.07 to 14.55), and 14.51 mg \u00b7 h\/liter (11.48 to 20.42) with dosages of 0.4, 0.7, and 1.0 mg\/kg q24h, respectively. DAmB PK is described adequately by a linear model that incorporates weight with clearance and volume. Interpatient PK variability is modest and unlikely to be responsible for variability in clinical outcomes. There is discordance between the impact that drug exposure has on CSF sterility and its impact on mortality outcomes, which may be due to cerebral pathology not reflected in CSF fungal burden, in addition to clinical variables.<\/jats:p>","DOI":"10.1128\/aac.02526-17","type":"journal-article","created":{"date-parts":[[2018,5,7]],"date-time":"2018-05-07T09:36:31Z","timestamp":1525685791000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Population Pharmacokinetic Model and Meta-analysis of Outcomes of Amphotericin B Deoxycholate Use in Adults with Cryptococcal Meningitis"],"prefix":"10.1128","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7079-7957","authenticated-orcid":false,"given":"Katharine E.","family":"Stott","sequence":"first","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics Laboratory, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"},{"name":"Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Beardsley","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Whalley","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics Laboratory, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Freddie Mukasa","family":"Kibengo","sequence":"additional","affiliation":[{"name":"MRC\/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguyen Thi Hoang","family":"Mai","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nguy\u1ec5n L\u00ea Nhu'","family":"T\u00f9ng","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngo Thi Kim","family":"Cuc","sequence":"additional","affiliation":[{"name":"Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruwanthi","family":"Kolamunnage-Dona","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Hope","sequence":"additional","affiliation":[{"name":"Antimicrobial Pharmacodynamics and Therapeutics Laboratory, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy","family":"Day","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30243-8"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/588792"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e3283536a93"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit794"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110404"},{"key":"e_1_3_3_7_2","first-page":"579","article-title":"Amphotericins A and B, antifungal antibiotics produced by a streptomycete. 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