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Journal Article > Commentary

Disease-specific differences in pharmacokinetics of paromomycin and miltefosine between post-kala-azar dermal leishmaniasis and visceral leishmaniasis patients in eastern Africa

Chu WY, Verrest L, Younis BM, Musa AM, Mbui J, Mohammed R, Olobo J, Ritmeijer K, Monnerat S, Wasunna M, Roseboom IC, Solomos A, Huitema ADR, Alves F, Dorlo TPC
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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%CI: 0.41-0.74) lower capacity for paromomycin saturable reabsorption in renal tubules, and required a 1.44-fold (1.23-1.71) adjustment when relating renal clearance to creatinine-based eGFR. Miltefosine bioavailability in VL patients was lowered by 69% (62-76) at treatment start. Comparing PKDL to VL patients on the same regimen, paromomycin plasma exposures were 0.74-0.87-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.

Countries
EthiopiaKenyaUgandaSudan
Subject Area
kala azarleishmaniasiscutaneous leishmaniasispharmacokinetics
DOI
10.1093/infdis/jiae413
Published Date
16-Dec-2024
PubMed ID
39166299
Languages
English
Journal
Journal of Infectious Diseases
Volume / Issue / Pages
Volume 230, Issue 6, Pages e1375-1384
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