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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 2/2008

01-02-2008 | Review Article

Clinical Pharmacology of Artemisinin-Based Combination Therapies

Authors: Prof. Francesca T. Aweeka, Polina I. German

Published in: Clinical Pharmacokinetics | Issue 2/2008

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Abstract

Malaria, a disease transmitted by the female Anopheles mosquito, has had devastating effects on human populations for more than 4000 years. Treatment of the disease with single drugs, such as chloroquine, sulfadoxine/pyrimethamine or mefloquine, has led to the emergence of resistant Plasmodium falciparum parasites that lead to the most severe form of the illness. Artemisinin-based combination therapies are currently recommended by WHO for the treatment of uncomplicated P. falciparum malaria. Artemisinin and semisynthetic derivatives, including artesunate, artemether and dihydroartemisinin, are short-acting antimalarial agents that kill parasites more rapidly than conventional antimalarials, and are active against both the sexual and asexual stages of the parasite cycle. Artemisinin fever clearance time is shortened to 32 hours as compared with 2–3 days with older agents. To delay or prevent emergence of resistance, artemisinins are combined with one of several longer-acting drugs — amodiaquine, mefloquine, sulfadoxine/pyrimethamine or lumefantrine — which permit elimination of the residual malarial parasites.
The clinical pharmacology of artemisinin-based combination therapies is highly complex. The short-acting artemisinins and their long-acting counterparts are metabolized and/or inhibit/induce cytochrome P450 enzymes, and may thus participate in drug-drug interactions with multiple drugs on the market. Alterations in antimalarial drug plasma concentrations may lead to either suboptimal efficacy or drug toxicity and may compromise treatment.
Footnotes
1
The use of trade names is for product identification purposes only and does not imply endorsement.
 
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Metadata
Title
Clinical Pharmacology of Artemisinin-Based Combination Therapies
Authors
Prof. Francesca T. Aweeka
Polina I. German
Publication date
01-02-2008
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 2/2008
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200847020-00002

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