Trial reportThe Journal of antimicrobial chemotherapy2017
Visceral leishmaniasis relapse hazard is linked to reduced miltefosine exposure in patients from Eastern Africa: a population pharmacokinetic/pharmacodynamic study.
Trial report in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Systematic Review of Host-Mediated Activity of Miltefosine in Leishmaniasis through Immunomodulation.Antimicrobial agents and chemotherapy · 2019Pooled it
- Population pharmacokinetics of a combination of miltefosine and paromomycin in Eastern African children and adults with visceral leishmaniasis.The Journal of antimicrobial chemotherapy · 2023Trial
- Paromomycin and Miltefosine Combination as an Alternative to Treat Patients With Visceral Leishmaniasis in Eastern Africa: A Randomized, Controlled, Multicountry Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Natural Resistance ofThe American journal of tropical medicine and hygiene · 2019Trial
- Pharmacokinetics, Safety, and Efficacy of an Allometric Miltefosine Regimen for the Treatment of Visceral Leishmaniasis in Eastern African Children: An Open-label, Phase II Clinical Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019Trial
- Macrophage Activation Marker Neopterin: A Candidate Biomarker for Treatment Response and Relapse in Visceral Leishmaniasis.Frontiers in cellular and infection microbiology · 2018Trial
- Weight-band-based simplification of oral allometric miltefosine dosing in paediatric patients with visceral leishmaniasis.The Journal of antimicrobial chemotherapy · 2026Article
- Post-kala-azar dermal leishmaniasis: insights into underlying pathogenic mechanisms and genetic landscape.Frontiers in microbiology · 2026Review
- The development of a global research agenda and individual participant data platform for visceral leishmaniasis: challenges and future opportunities.Parasites & vectors · 2025Article
- Disease-Specific Differences in Pharmacokinetics of Paromomycin and Miltefosine Between Post-Kala-Azar Dermal Leishmaniasis and Visceral Leishmaniasis Patients in Eastern Africa.The Journal of infectious diseases · 2024Article
- Determining tissue distribution of the oral antileishmanial agent miltefosine: a physiologically-based pharmacokinetic modeling approach.Antimicrobial agents and chemotherapy · 2024Article
- Skin pharmacokinetics of miltefosine in the treatment of post-kala-azar dermal leishmaniasis in South Asia.The Journal of antimicrobial chemotherapy · 2024Article
- Pharmacokinetics, Dose-Proportionality, and Tolerability of Intravenous Tanespimycin (17-AAG) in Single and Multiple Doses in Dogs: A Potential Novel Treatment for Canine Visceral Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Leishmania blood parasite dynamics during and after treatment of visceral leishmaniasis in Eastern Africa: A pharmacokinetic-pharmacodynamic model.PLoS neglected tropical diseases · 2024Article
- The Potential Use of Peptides in the Fight against Chagas Disease and Leishmaniasis.Pharmaceutics · 2024Review
- Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach.Pharmaceutical research · 2023Article
- Finding the right hazard function for time-to-event modeling: A tutorial and Shiny application.CPT: pharmacometrics & systems pharmacology · 2022Article
- In Vitro Susceptibility to Miltefosine ofMicroorganisms · 2021Article
- Low antileishmanial drug exposure in HIV-positive visceral leishmaniasis patients on antiretrovirals: an Ethiopian cohort study.The Journal of antimicrobial chemotherapy · 2021Article
- Pharmacokinetic / pharmacodynamic relationships of liposomal amphotericin B and miltefosine in experimental visceral leishmaniasis.PLoS neglected tropical diseases · 2021Article
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLow efficacy of miltefosine in the treatment of visceral leishmaniasis was recently observed in Eastern Africa.
objectivesTo describe the pharmacokinetics and establish a pharmacokinetic/pharmacodynamic relationship for miltefosine in Eastern African patients with visceral leishmaniasis, using a time-to-event approach to model relapse of disease.
methodsMiltefosine plasma concentrations from 95 patients (48 monotherapy versus 47 combination therapy) were included in the population pharmacokinetic model using non-linear mixed effects modelling. Subsequently a time-to-event model was developed to model the time of clinical relapse. Various summary pharmacokinetic parameters (various AUCs, Time > EC50, Time > EC90), normalized within each treatment arm to allow simultaneous analysis, were evaluated as relapse hazard-changing covariates.
resultsA two-compartment population model with first-order absorption fitted the miltefosine pharmacokinetic data adequately. Relative bioavailability was reduced (-74%, relative standard error 4.7%) during the first week of treatment of the monotherapy arm but only the first day of the shorter combination regimen. Time to the relapse of infection could be described using a constant baseline hazard (baseline 1.8 relapses/year, relative standard error 72.7%). Miltefosine Time > EC90 improved the model significantly when added in a maximum effect function on the baseline hazard (half maximal effect with Time > EC90 6.97 days for monotherapy).
conclusionsMiltefosine drug exposure was found to be decreased in Eastern African patients with visceral leishmaniasis, due to a (transient) initial lower bioavailability. Relapse hazard was inversely linked to miltefosine exposure. Significantly lower miltefosine exposure was observed in children compared with adults, further urging the need for implementation of dose adaptations for children.
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