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Quinolines interfere with heme-mediated activation of artemisinins.
bioRxiv
August 2025
Division of Infectious Diseases, Washington University School of Medicine, Saint Louis, MO United States of America.
Artemisinin-based combination therapies (ACTs) remain the mainstay of treatment for malaria, despite reports of ACT treatment failure. ACTs consist of an artemisinin and a longer-lived partner drug, which is often a quinoline. Given that heme is central to the mechanism of action of artemisinins and some quinolines, we hypothesized that these antimalarials would exhibit strong drug-drug interactions.
View Article and Find Full Text PDFSingle low dose primaquine to block the transmission of Plasmodium falciparum-proposed stand-alone and ACT-adapted regimens.
BMC Med
July 2025
Mahidol Oxford Tropical Medicine Research Unit (MORU), Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok, 10400, Thailand.
Background: Despite the 2012 WHO recommendation to add single low dose primaquine (SLDPQ, 0.25 mg/kg body weight) to artemisinin-based combination treatments (ACTs) for blocking the transmission of artemisinin-resistant Plasmodium falciparum, there are currently no weight-based regimens founded on robust evidence.
Methods: Applying published safety, transmission blocking and pharmacokinetic data, and exploring pharmacokinetic-pharmacodynamic relationships of age-based dosing of SLDPQ in African children with acute, uncomplicated Plasmodium falciparum, we derived weight-based, stand-alone, ACT-, triple ACT-, and vivax-matched regimens by following allometric dosing principles and simulating PQ exposure (area under the concentration time curve).
Slowing the spread of treatment failure to artemisinin-based combination therapies in Uganda.
medRxiv
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Institute for Genomics and Evolutionary Medicine, Department of Biology, Temple University, Philadelphia, PA, USA.
Background: The multiple emergences and continuing spread of partially artemisinin-resistant in Africa, where about 95% of malaria occurs, is a health challenge that requires urgent attention. The World Health Organization has developed a resistance response strategy that centers on enhancing surveillance, reducing drug pressure, and evaluating novel tools to slow resistance evolution which includes the deployment of multiple first-line therapies (MFT). Developing a specific resistance response is critical for Uganda, where four mutations are at local allele frequencies >0.
View Article and Find Full Text PDFMultiplex LC-MS/MS assay for simultaneous quantification of artesunate and its active metabolite dihydroartemisinin with pyronaridine, proguanil, cycloguanil, and clindamycin in pharmacokinetic studies.
Malar J
May 2025
Institute of Pharmacy, Department of Clinical Pharmacy, University of Hamburg, Hamburg, Germany.
Background: Malaria, especially caused by Plasmodium falciparum, remains a major global health concern, particularly in sub-Saharan Africa. To combat rising drug resistance, innovative treatment approaches like triple artemisinin-based combination therapy (TACT) and multi-drug antimalarial combination therapies (MDACTs) are being explored.
Methods: This study introduces a robust and validated multiplex LC-MS/MS assay for the simultaneous quantification of key antimalarial drugs and their metabolites, including artesunate, dihydroartemisinin, pyronaridine, proguanil, cycloguanil, and clindamycin.
Dose-Optimization of a Novel Co-Formulated Triple Combination Antimalarial Therapy: Artemether-Lumefantrine-Amodiaquine.
Clin Pharmacol Ther
May 2025
Mahidol Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Artemisinin-based combination therapy (ACT) is the first-line therapy for uncomplicated falciparum malaria, but artemisinin resistance in Asia and now sub-Saharan Africa is threatening our ability to control and eliminate malaria. Triple-ACTs have emerged as a viable alternative treatment to combat declining ACT efficacy due to drug-resistant malaria. In this study, we developed and evaluated an optimal fixed-dose regimen of artemether-lumefantrine-amodiaquine through population pharmacokinetic modeling and simulation.
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