Evidence map›Paper›PMID 39166299›Full record

ArticleThe Journal of infectious diseases2024

Disease-Specific Differences in Pharmacokinetics of Paromomycin and Miltefosine Between Post-Kala-Azar Dermal Leishmaniasis and Visceral Leishmaniasis Patients in Eastern Africa.

Wan-Yu Chu, Luka Verrest, Brima M Younis, Ahmed M Musa, Jane Mbui, Rezika Mohammed, Joseph Olobo, Koert Ritmeijer, Séverine Monnerat, Monique Wasunna and 5 more

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Wan-Yu ChuDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-0402-8807
Luka VerrestDepartment of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Brima M YounisInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Ahmed M MusaInstitute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Jane MbuiCentre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya.
Rezika MohammedLeishmaniasis Research and Treatment Center, University of Gondar, Gondar, Ethiopia.
Joseph OloboDepartment of Immunology and Molecular Biology, Makerere University, Kampala, Uganda.
Koert RitmeijerMédecins Sans Frontières, Amsterdam, The Netherlands.
Séverine MonneratDrugs for Neglected Diseases initiative, Geneva, Switzerland.
Monique WasunnaDrugs for Neglected Diseases initiative, Nairobi, Kenya.
Ignace C RoseboomDepartment of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Alexandra SolomosDrugs for Neglected Diseases initiative, Geneva, Switzerland.
Alwin D R HuitemaDepartment of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
Fabiana AlvesDrugs for Neglected Diseases initiative, Geneva, Switzerland.
Thomas P C DorloDepartment of Pharmacy, Uppsala University, Uppsala, Sweden.ORCID 0000-0003-3076-8435

Funding

Dutch Ministry of Foreign AffairsDutch Research Council 91617140European and Developing Countries Clinical Trials PartnershipEuropean Union RIA2016S-1635Federal Ministry of Education and ResearchKfW, GermanyMédecins sans Frontières InternationalMedicor FoundationSwedish Research Council VR 2022-01251Swiss Agency for Development and Cooperation
6 · The paper itself

Abstract

Treatment regimens for post-kala-azar dermal leishmaniasis (PKDL) are usually extrapolated from those for visceral leishmaniasis (VL), but drug pharmacokinetics (PK) can differ due to disease-specific variations in absorption, distribution, and elimination. 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-.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (95% CI, 1.23-1.71) adjustment when relating renal clearance to creatinine-based estimated glomerular filtration rate. Miltefosine bioavailability in VL patients was lowered by 69% (95% CI, 62%-76%) 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.

Indexed as

Antiprotozoal AgentsLeishmaniasis, CutaneousLeishmaniasis, VisceralParomomycinPhosphorylcholineAdolescentAdultAfrica, EasternAgedChildFemaleHumansMaleMiddle AgedYoung AdultAntiprotozoal AgentsmiltefosineParomomycinPhosphorylcholinemiltefosineparomomycinpharmacokineticspost-kala-azar dermal leishmaniasisvisceral leishmaniasis

Identifiers

PMID39166299
PMCPMC11646621

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.