Dose-Optimization of a Novel Co-Formulated Triple Combination Antimalarial Therapy: Artemether-Lumefantrine-Amodiaquine
Issued Date
2025-01-01
Resource Type
ISSN
00099236
eISSN
15326535
DOI
Scopus ID
2-s2.0-85217716114
Journal Title
Clinical Pharmacology and Therapeutics
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SCOPUS
Bibliographic Citation
Clinical Pharmacology and Therapeutics (2025)
Suggested Citation
Tarning J., White N.J., Dondorp A.M. Dose-Optimization of a Novel Co-Formulated Triple Combination Antimalarial Therapy: Artemether-Lumefantrine-Amodiaquine. Clinical Pharmacology and Therapeutics (2025). doi:10.1002/cpt.3582 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/105372
Title
Dose-Optimization of a Novel Co-Formulated Triple Combination Antimalarial Therapy: Artemether-Lumefantrine-Amodiaquine
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Abstract
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. Three published population-based pharmacometric models and two large cohorts of observed adult subjects and pediatric malaria patients were used to simulate pharmacokinetic profiles of different dosing strategies. Based on simulated total exposure and peak concentrations, an optimal dose regimen was developed resulting in an extension of the current 4 weight bands to a total of 5 weight bands to generate equivalent exposures in all body weight groups and minimize the fluctuation in exposure between patients. The proposed drug-to-drug ratio of artemether-lumefantrine-amodiaquine (20:120:40 mg) was kept constant throughout the dosing bands in order to simplify manufacturing, implementation, and further development of a fixed-dose co-formulated product.