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Randomized Controlled Trial
. 2022 Oct 2;15(1):313.
doi: 10.1186/s13104-022-06212-y.

Modelling the optimal dosing schedule for artemether-lumefantrine chemoprophylaxis against malaria

Joel Tarning  1   2 , Lorenz von Seidlein  1   2 , Arjen M Dondorp  1   2 , Nicholas J White  1   2 , Richard J Maude  3   4   5   6
Affiliations
Randomized Controlled Trial

Modelling the optimal dosing schedule for artemether-lumefantrine chemoprophylaxis against malaria

Joel Tarning et al. BMC Res Notes. .

Abstract

Objective: Antimalarial chemoprophylaxis for high risk groups in endemic areas of Southeast Asia has the potential to reduce malaria transmission and accelerate elimination. However, the optimal choice of medication and dosing for many potential candidates is not clear. For a planned randomised controlled trial of prophylaxis for forest goers in Cambodia, artemether-lumefantrine (AL) was selected because of its ongoing efficacy and excellent tolerability and safety. As AL had not been used before for this purpose, a previously published pooled pharmacometric meta-model was used to determine the optimal dosing schedule.

Results: A full 3 day AL treatment course given twice a month, and twice daily treatment given once a week, resulted in trough concentrations consistently above the therapeutic threshold of 200 ng/mL. However, the most favourable exposure profile, and arguably most practical dosing scenario, was an initial 3 day full AL treatment course followed by twice daily dosing given once a week for the duration of chemoprevention. The latter was adopted as the dosing schedule for the trial.

Keywords: artemether; lumefantrine; malaria; modelling; pharmacometric; prophylaxis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Predicted lumefantrine concentrations simulating different dosing schedules. Panel a) shows a full 3 day treatment course of 480 mg lumefantrine given once a month. Panel b) shows a full 3 day treatment course of 480 mg lumefantrine given twice a month. Panel c) shows a loading dose of a full 3 day treatment course of 480 mg lumefantrine followed by 480 mg lumefantrine QD given once a week. Panel d) shows a loading dose of a full 3 day treatment course of 480 mg lumefantrine followed by 480 mg lumefantrine BID given once a week
See this image and copyright information in PMC

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