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This study characterized PK differences in paromomycin and miltefosine between 109 PKDL and 264 VL patients from Eastern Africa. VL patients showed 0.55-fold (95% confidence interval [CI], .41\u2013.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (95% CI, 1.23\u20131.71) adjustment when relating renal clearance to creatinine-based estimated glomerular filtration rate. Miltefosine bioavailability in VL patients was lowered by 69% (95% CI, 62%\u201376%) at treatment start. Comparing PKDL to VL patients on the same regimen, paromomycin plasma exposures were 0.74- to 0.87-fold, while miltefosine exposure until the end of treatment day was 1.4-fold. These pronounced PK differences between PKDL and VL patients in Eastern Africa highlight the challenges of directly extrapolating dosing regimens from one leishmaniasis presentation to another.<\/jats:p>","DOI":"10.1093\/infdis\/jiae413","type":"journal-article","created":{"date-parts":[[2024,8,16]],"date-time":"2024-08-16T10:18:23Z","timestamp":1723803503000},"page":"e1375-e1384","source":"Crossref","is-referenced-by-count":7,"title":["Disease-Specific Differences in Pharmacokinetics of Paromomycin and Miltefosine Between Post-Kala-Azar Dermal Leishmaniasis and Visceral Leishmaniasis Patients in Eastern Africa"],"prefix":"10.1093","volume":"230","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0402-8807","authenticated-orcid":false,"given":"Wan-Yu","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Uppsala University , Uppsala ,","place":["Sweden"]},{"name":"Department of Pharmacy and Pharmacology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luka","family":"Verrest","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brima M","family":"Younis","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum , Khartoum ,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M","family":"Musa","sequence":"additional","affiliation":[{"name":"Institute of Endemic Diseases, University of Khartoum , Khartoum ,","place":["Sudan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Mbui","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research, Kenya Medical Research Institute , Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rezika","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Leishmaniasis Research and Treatment Center, University of Gondar , Gondar,","place":["Ethiopia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Olobo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Molecular Biology, Makerere University , Kampala ,","place":["Uganda"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koert","family":"Ritmeijer","sequence":"additional","affiliation":[{"name":"M\u00e9decins Sans Fronti\u00e8res , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Monnerat","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique","family":"Wasunna","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative , Nairobi ,","place":["Kenya"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignace C","family":"Roseboom","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Solomos","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin D R","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Pharmacology, Netherlands Cancer Institute , Amsterdam ,","place":["The Netherlands"]},{"name":"Department of Pharmacology, Princess M\u00e1xima Center for Pediatric Oncology, Utrecht, The Netherlands"},{"name":"Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University ,","place":["Utrecht, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Alves","sequence":"additional","affiliation":[{"name":"Drugs for Neglected Diseases initiative , Geneva ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3076-8435","authenticated-orcid":false,"given":"Thomas P C","family":"Dorlo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Uppsala University , Uppsala ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,21]]},"reference":[{"key":"2024121523525460800_jiae413-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? 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