{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:50:42Z","timestamp":1792698642172,"version":"4.5.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2017,9,6]],"date-time":"2017-09-06T00:00:00Z","timestamp":1504656000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000278","name":"DFID","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000278","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007729","name":"Dutch Ministry of Foreign Affairs","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007729","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"BMBF","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009131","name":"Swiss Agency for Development and Cooperation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009131","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Netherlands Organisation for Scientific Research","doi-asserted-by":"publisher","award":["91617140"],"award-info":[{"award-number":["91617140"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,11,1]]},"DOI":"10.1093\/jac\/dkx283","type":"journal-article","created":{"date-parts":[[2017,8,4]],"date-time":"2017-08-04T07:08:39Z","timestamp":1501830519000},"page":"3131-3140","source":"Crossref","is-referenced-by-count":33,"title":["Visceral leishmaniasis relapse hazard is linked to reduced miltefosine exposure in patients from Eastern Africa: a population pharmacokinetic\/pharmacodynamic study"],"prefix":"10.1093","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3076-8435","authenticated-orcid":false,"given":"Thomas P C","family":"Dorlo","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"},{"name":"Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital\/Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke E","family":"Kip","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital\/Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brima M","family":"Younis","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally J","family":"Ellis","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Alves","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos. H","family":"Beijnen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy & Pharmacology, Antoni van Leeuwenhoek Hospital\/Netherlands Cancer Institute, Amsterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Njenga","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kirigi","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asrat","family":"Hailu","sequence":"additional","affiliation":[{"name":"Addis Ababa University, Addis Ababa, Ethiopia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Olobo","sequence":"additional","affiliation":[{"name":"Makerere University, Kampala, Uganda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M","family":"Musa","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manica","family":"Balasegaram","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Wasunna","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mats O","family":"Karlsson","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eltahir A G","family":"Khalil","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,6]]},"reference":[{"key":"key\n\t\t\t\t20180328153133_dkx283-B1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.4269\/ajtmh.2011.10-0321","article-title":"Who is a typical patient with visceral leishmaniasis? Characterizing the demographic and nutritional profile of patients in Brazil, East Africa, and South Asia","volume":"84","author":"Harhay","year":"2011","journal-title":"Am J Trop Med Hyg"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/j.1365-3156.2009.02279.x","article-title":"The poorest of the poor: a poverty appraisal of households affected by visceral leishmaniasis in Bihar, India","volume":"14","author":"Boelaert","year":"2009","journal-title":"Trop Med Int Health"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B3","doi-asserted-by":"crossref","first-page":"e35671.","DOI":"10.1371\/journal.pone.0035671","article-title":"Leishmaniasis worldwide and global estimates of its incidence","volume":"7","author":"Alvar","year":"2012","journal-title":"PLoS One"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B4","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1093\/cid\/cit102","article-title":"Increasing failure of miltefosine in the treatment of Kala-azar in Nepal and the potential role of parasite drug resistance, reinfection, or noncompliance","volume":"56","author":"Rijal","year":"2013","journal-title":"Clin Infect Dis"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B5","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.1093\/jac\/dks275","article-title":"Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis","volume":"67","author":"Dorlo","year":"2012","journal-title":"J Antimicrob Chemother"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B6","doi-asserted-by":"crossref","first-page":"e0004880.","DOI":"10.1371\/journal.pntd.0004880","article-title":"Efficacy and safety of AmBisome in combination with sodium stibogluconate or miltefosine and miltefosine monotherapy for african visceral leishmaniasis: phase II randomized trial","volume":"10","author":"Wasunna","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B7","doi-asserted-by":"crossref","first-page":"e2613","DOI":"10.1371\/journal.pntd.0002613","article-title":"Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial","volume":"8","author":"Khalil","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B8","doi-asserted-by":"crossref","first-page":"e1674.","DOI":"10.1371\/journal.pntd.0001674","article-title":"Sodium stibogluconate (SSG) & paromomycin combination compared to SSG for visceral leishmaniasis in East Africa: a randomised controlled trial","volume":"6","author":"Musa","year":"2012","journal-title":"PLoS Negl Trop Dis"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B9","doi-asserted-by":"crossref","first-page":"3864","DOI":"10.1128\/AAC.00292-12","article-title":"Optimal dosing of miltefosine in children and adults with visceral leishmaniasis","volume":"56","author":"Dorlo","year":"2012","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B10","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/infdis\/jiu039","article-title":"Failure of miltefosine in visceral leishmaniasis is associated with low drug exposure","volume":"210","author":"Dorlo","year":"2014","journal-title":"J Infect Dis"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B11","doi-asserted-by":"crossref","first-page":"2855","DOI":"10.1128\/AAC.00014-08","article-title":"Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients","volume":"52","author":"Dorlo","year":"2008","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B12","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02198-16","article-title":"Pharmacokinetics of miltefosine in children and adults with cutaneous leishmaniasis","volume":"61","author":"Castro","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B13","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jchromb.2008.02.005","article-title":"Development and validation of a quantitative assay for the measurement of miltefosine in human plasma by liquid chromatography-tandem mass spectrometry","volume":"865","author":"Dorlo","year":"2008","journal-title":"J Chromatogr B"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B14","volume-title":"NONMEM User\u2019s Guides","author":"Beal","year":"2009"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B15","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Development Core Team","year":"2014"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B16","doi-asserted-by":"crossref","first-page":"e50.","DOI":"10.1038\/psp.2013.24","article-title":"Modeling and simulation workbench for NONMEM: tutorial on Pirana, PsN, and Xpose","volume":"2","author":"Keizer","year":"2013","journal-title":"CPT Pharmacometrics Syst Pharmacol"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B17","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1023\/A:1012299115260","article-title":"Ways to fit a PK model with some data below the quantification limit","volume":"28","author":"Beal","year":"2001","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s10928-008-9094-4","article-title":"Likelihood based approaches to handling data below the quantification limit using NONMEM VI","volume":"35","author":"Ahn","year":"2008","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B19","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.2165\/00003088-200544100-00004","article-title":"Quantification of lean bodyweight","volume":"44","author":"Janmahasatian","year":"2005","journal-title":"Clin Pharmacokinet"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B20","doi-asserted-by":"crossref","first-page":"68","DOI":"10.2165\/00003088-198900171-00006","article-title":"Drug metabolism and pharmacokinetics in malnourished children","volume":"17","author":"Krishnaswamy","year":"1989","journal-title":"Clin Pharmacokinet"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1007\/BF01071974","article-title":"Intestinal malabsorption in malnourished children before and during recovery. Relation between severity of protein deficiency and the malabsorption process","volume":"18","author":"Viteri","year":"1973","journal-title":"Am J Dig Dis"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B22","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1111\/j.1365-2125.1987.tb03077.x","article-title":"Single dose disposition of chloroquine in kwashiorkor and normal children\u2014evidence for decreased absorption in kwashiorkor","volume":"23","author":"Walker","year":"1987","journal-title":"Br J Clin Pharmacol"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B23","doi-asserted-by":"crossref","first-page":"e63","DOI":"10.1097\/INF.0000000000000603","article-title":"The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda","volume":"34","author":"Bartelink","year":"2015","journal-title":"Pediatr Infect Dis J"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B24","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/BF00607094","article-title":"Chloramphenicol pharmacokinetics in Ethiopian children of differing nutritional status","volume":"24","author":"Eriksson","year":"1983","journal-title":"Eur J Clin Pharmacol"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B25","doi-asserted-by":"crossref","first-page":"3793","DOI":"10.1128\/AAC.00837-06","article-title":"Interaction between Miltefosine and amphotericin B: consequences for their activities towards intestinal epithelial cells and Leishmania donovani promastigotes in vitro","volume":"50","author":"M\u00e9nez","year":"2006","journal-title":"Antimicrob Agents Chemother"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B26","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.biopha.2005.09.001","article-title":"A liposomal formulation of doxorubicin, composed of hexadecylphosphocholine (HePC): physicochemical characterization and cytotoxic activity against human cancer cell lines","volume":"60","author":"Papagiannaros","year":"2006","journal-title":"Biomed Pharmacother"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B27","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1093\/jac\/dkp321","article-title":"Membrane sterol depletion impairs miltefosine action in wild-type and miltefosine-resistant Leishmania donovani promastigotes","volume":"64","author":"Saint-Pierre-Chazalet","year":"2009","journal-title":"J Antimicrob Chemother"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2133\/dmpk.24.25","article-title":"Mechanistic basis of using body size and maturation to predict clearance in humans","volume":"24","author":"Anderson","year":"2009","journal-title":"Drug Metab Pharmacokinet"},{"key":"key\n\t\t\t\t20180328153133_dkx283-B29","doi-asserted-by":"crossref","first-page":"e100220","DOI":"10.1371\/journal.pone.0100220","article-title":"Failure of miltefosine treatment for visceral leishmaniasis in children and men in South-East Asia","volume":"9","author":"Ostyn","year":"2014","journal-title":"PLoS One"}],"container-title":["Journal of Antimicrobial Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jac\/article-pdf\/72\/11\/3131\/24332197\/dkx283.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,3,28]],"date-time":"2018-03-28T20:00:15Z","timestamp":1522267215000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jac\/article\/72\/11\/3131\/4106324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,6]]},"references-count":29,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2017,9,6]]},"published-print":{"date-parts":[[2017,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jac\/dkx283","relation":{},"ISSN":["0305-7453","1460-2091"],"issn-type":[{"value":"0305-7453","type":"print"},{"value":"1460-2091","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2017,11]]},"published":{"date-parts":[[2017,9,6]]}}}