Modified Fixed-ratio Isobologram Method for Studying in Vitro Interactions Between Atovaquone and Proguanil or Dihydroartemisinin Against Drug-resistant Strains of Plasmodium Falciparum

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2004 Oct 27

PMID 15504827

Citations 154

Authors

Quinton L Fivelman

Ipemida S Adagu

David C Warhurst

Affiliations

Soon will be listed here.

Abstract

A modified fixed-ratio isobologram method for studying the in vitro interactions between antiplasmodial drugs is described. This method was used to examine the interactions between atovaquone, proguanil, and dihydroartemisinin. The interaction between atovaquone and proguanil was synergistic against atovaquone-sensitive strains K1 and T996; however, there was a loss of synergy against atovaquone-resistant strain NGATV01 isolated after Malarone (the combination of atovaquone and proguanil) treatment failure. While the interaction between atovaquone and dihydroartemisinin was indifferent against isolate NGATV01, the interaction displayed indifference tending toward antagonism against the atovaquone-sensitive strains tested. The relevance of in vitro interactions to in vivo treatment is discussed.

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