ArticleThe Journal of antimicrobial chemotherapy2018
Pharmacodynamics and cellular accumulation of amphotericin B and miltefosine in Leishmania donovani-infected primary macrophages.
Article in The Journal of antimicrobial chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress.EMBO reports · 2023Article
- Effect of topical berberine in murine cutaneous leishmaniasis lesions.The Journal of antimicrobial chemotherapy · 2022Article
- Delivery strategies of amphotericin B for invasive fungal infections.Acta pharmaceutica Sinica. B · 2021Review
- Leishmaniasis immunopathology-impact on design and use of vaccines, diagnostics and drugs.Seminars in immunopathology · 2020Review
- Novel and safe single-dose treatment of cutaneous leishmaniasis with implantable amphotericin B-loaded microparticles.International journal for parasitology. Drugs and drug resistance · 2019Article
- Challenges in drug discovery targeting TriTryp diseases with an emphasis on leishmaniasis.International journal for parasitology. Drugs and drug resistance · 2018Review
- Impact of primary mouse macrophage cell types on Leishmania infection and in vitro drug susceptibility.Parasitology research · 2018Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Objectives: We examined the in vitro pharmacodynamics and cellular accumulation of the standard anti-leishmanial drugs amphotericin B and miltefosine in intracellular Leishmania donovani amastigote-macrophage drug assays. Methods: Primary mouse macrophages were infected with L. donovani amastigotes. In time-kill assays infected macrophages were exposed to at least six different concentrations of serially diluted drugs and the percentage of infected macrophages was determined after 6, 12, 24, 48, 72 and 120 h of exposure. Cellular drug accumulation was measured following exposure to highly effective drug concentrations for 1, 6, 24, 48 and 72 h. Data were analysed through a mathematical model, relating drug concentration to the percentage of infected cells over time. Host cell membrane damage was evaluated through measurement of lactate dehydrogenase release. The effect of varying the serum and albumin concentrations in medium on the cellular accumulation levels of miltefosine was measured. Results: Amphotericin B was more potent than miltefosine (EC50 values of 0.65 and 1.26 μM, respectively) and displayed a wider therapeutic window in vitro. The kinetics of the cellular accumulation of amphotericin B was concentration- and formulation-dependent. At an extracellular concentration of 10 μM miltefosine maximum cellular drug levels preceded maximum anti-leishmanial kill. Miltefosine induced membrane damage in a concentration-, time- and serum-dependent manner. Its cellular accumulation levels increased with decreasing amounts of protein in assay medium. Conclusions: We have developed a novel approach to investigate the cellular pharmacology of anti-leishmanial drugs that serves as a model for the characterization of new drug candidates.
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Registered trials
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.