Clinical Pharmacokinetics

, Volume 37, Issue 2, pp 105–125

Clinical Pharmacokinetics and Pharmacodynamics of Artemether-Lumefantrine

Authors

    • Faculty of Tropical MedicineMahidol University
    • Department of Infectious DiseasesTropical Medicine and AIDS, Academic Medical Centre
    • Centre for Tropical Medicine, Nuffield Department of MedicineUniversity of Oxford
  • Michele van Vugt
    • Faculty of Tropical MedicineMahidol University
    • Department of Infectious DiseasesTropical Medicine and AIDS, Academic Medical Centre
    • Shoklo Malaria Research Unit
  • Farka D Ezzet
    • Novartis Pharma AG
Review Articles Drug Disposition

DOI: 10.2165/00003088-199937020-00002

Cite this article as:
White, N.J., van Vugt, M. & Ezzet, F.D. Clin Pharmacokinet (1999) 37: 105. doi:10.2165/00003088-199937020-00002

Abstract

The combination of artemether and lumefantrine (benflumetol) is a new and very well tolerated oral antimalarial drug effective even against multidrug-resistant falciparum malaria. The artemether component is absorbed rapidly and biotransformed to dihydroartemisinin, and both are eliminated with terminal half-lives of around 1 hour. These are very active antimalarials which give a rapid reduction in parasite biomass and consequent rapid resolution of symptoms. The lumefantrine component is absorbed variably in malaria, and is eliminated more slowly (half-life of 3 to 6 days). Absorption is very dependent on coadministration with fat, and so improves markedly with recovery from malaria. Thus artemether clears most of the infection, and the lumefantrine concentrations that remain at the end of the 3- to 5-day treatment course are responsible for eliminating the residual 100 to 10 000 parasites. The area under the curve of plasma lumefantrine concentrations versus time, or its correlate the plasma concentration on day 7, has proved an important determinant of therapeutic response. Characterisation of these pharmacokinetic-pharmacodynamic relationships provided the basis for dosage optimisation, an approach that could be applied to other antimalarial drugs.

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© Adis International Limited 1999