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Title: Clinical pharmacokinetics and pharmacodynamics of artemether-lumefantrine
Authors: Nicholas J. White
Michele Van Vugt
Farkad Ezzet
Mahidol University
Academic Medical Centre, University of Amsterdam
Nuffield Department of Clinical Medicine
Shoklo Malaria Research Unit
Novartis International AG
Keywords: Medicine;Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jan-1999
Citation: Clinical Pharmacokinetics. Vol.37, No.2 (1999), 105-125
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.
ISSN: 03125963
Appears in Collections:Scopus 1991-2000

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