ArticleThe Journal of antimicrobial chemotherapy2020
Characterizing the non-linear pharmacokinetics of miltefosine in paediatric visceral leishmaniasis patients from Eastern Africa.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Influence of Malnutrition on the Pharmacokinetics of Drugs Used in the Treatment of Poverty-Related Diseases: A Systematic Review.Clinical pharmacokinetics · 2021Pooled 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
- Weight-band-based simplification of oral allometric miltefosine dosing in paediatric patients with visceral leishmaniasis.The Journal of antimicrobial chemotherapy · 2026Article
- Labeling Pediatric Products: BPCA Efforts and Orphan Drug Opportunities.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2025Article
- Evaluation of Beauvericin's activity and mode of action against all life stages ofFrontiers in cellular and infection microbiology · 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
- Leishmania blood parasite dynamics during and after treatment of visceral leishmaniasis in Eastern Africa: A pharmacokinetic-pharmacodynamic model.PLoS neglected tropical diseases · 2024Article
- Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach.Pharmaceutical research · 2023Article
- Cutaneous leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study.PLoS neglected tropical diseases · 2023Article
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Authors and funding
10 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundConventional miltefosine dosing (2.5 mg/kg/day) for treatment of visceral leishmaniasis (VL) is less effective in children than in adults. A higher allometric dose (median 3.2 mg/kg/day) was therefore investigated in paediatric VL patients in Eastern Africa. Results of this trial showed an unforeseen, lower than dose-proportional increase in exposure. Therefore, we performed a pooled model-based analysis of the paediatric data available from both dosing regimens to characterize observed non-linearities in miltefosine pharmacokinetics (PK).
methodsFifty-one children with VL were included in this analysis, treated with either a conventional (n = 21) or allometric (n = 30) miltefosine dosing regimen. PK data were analysed using non-linear mixed-effects modelling.
resultsA two-compartment model following first-order absorption and linear elimination, with two separate effects on relative oral bioavailability, was found to fit these data best. A 69% lower bioavailability at treatment start was estimated, presumably due to initial malnourishment and malabsorption. Stagnation in miltefosine accumulation in plasma, hampering increased drug exposure, was related to the increase in cumulative dose (mg/kg/day). However, the allometric regimen increased exposure 1.7-fold in the first treatment week and reduced the time to reach the PK target by 17.4%.
conclusionsMiltefosine PK in children suffering from VL are characterized by dose-dependent non-linearities that obstruct the initially expected exposure levels. Bioavailability appeared to be affected by the cumulative dose, possibly as a consequence of impaired absorption. Despite this, allometric dosing led to a faster target achievement and increased exposure compared with conventional dosing.
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