Pharmacokinetics and Pharmacodynamics of Antimalarial Drugs Used in Combination Therapy

Clinical Significance of Antimalarial Combinations

Author(s): Qigui Li and Mark R. Hickman

Pp: 63-94 (32)

DOI: 10.2174/9781681080543115010007

* (Excluding Mailing and Handling)

Abstract

Combination therapies composed of new antimalarial therapeutics with distinctly different parasite targets and mechanisms of action are the best tools to enhance treatment of uncomplicated falciparum malaria and delay the appearance and expansion of drug resistant malaria. The efficacy of artemisinin combination therapies is the most relevant criteria for evaluating drug combinations. The demonstrated values of an ACT to improve clinical outcomes and delay emergence and spread of parasite drug resistance were all factors in the decision by the WHO to recommend that ACTs be used as the best treatment for treating uncomplicated infections with P. falciparum malaria in Asia and Africa. As discussed in the last chapter, the list of recommended ACTs includes dihydroartemisinin-piperaquine, artemether-lumefantrine, artesunate-mefloquine, artesunate-sulfadoxine-pyrimethamine, and artesunate-amodiaquine. All of these combinations have been shown to be efficacious; however, efficacy of an ACT is affected by resistance to either drug partner. The cost of artemisinin analogues derivatives is a significant contributor to the increased cost of ACT treatment courses. A research project called the artemisinin project was initiated to develop an inexpensive method of semisynthetic production of artemisinins through fermentation rather than deriving artemisinin analogues by extracting artemisinin from the sweet wormwood plant. A cheaper manufacturing method will make ACTs more affordable, and it will be possible to increase distribution to patients in need. Innovations that facilitate production of cheaper ACTs will enhance the odds of a full recovery from falciparum malaria infections with decreased side effects and limit the emergence and spread of drug resistant parasites. Through vigorous efforts to enhance manufacture of inexpensive artemisinins coupled with improved prescription and enhanced patient compliance, the artemisinin drug combinations may still be effective for decades to come.


Keywords: Action mode, adverse effects, Artemether- lumefantrine, artesunateamodiaquine, artesunate-mefloquine, clinical recovery, dihydroartemisininpiperaquine, low cost, parasitological cure, therapeutic efficacy.

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