Abstract
The interaction between atovaquone and proguanil has never been studied against liver stage malaria, which is the main target of this drug combination when used for chemoprevention. Using human hepatocytes lacking cytochrome P450 activity, and thus avoiding proguanil metabolizing into potent cycloguanil, we show in vitro that the atovaquone-proguanil combination synergistically inhibits the growth of rodent Plasmodium yoelii parasites. These results provide a pharmacological basis for the high efficacy of atovaquone-proguanil used as malaria chemoprevention.
Copyright © 2016, American Society for Microbiology. All Rights Reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antimalarials / therapeutic use*
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Atovaquone / therapeutic use*
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Drug Combinations
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Hepatocytes / parasitology*
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Humans
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Inhibitory Concentration 50
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Liver / parasitology*
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Malaria, Falciparum / drug therapy*
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Malaria, Falciparum / prevention & control*
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Plasmodium falciparum / drug effects
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Plasmodium falciparum / pathogenicity
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Proguanil / therapeutic use*
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Triazines / therapeutic use
Substances
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Antimalarials
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Drug Combinations
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Triazines
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atovaquone, proguanil drug combination
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cycloguanil
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Proguanil
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Atovaquone
Grants and funding
Neither funder had a role in study design, data analysis, data interpretation, or data reporting.