Modified fixed-ratio isobologram method for studying in vitro interactions between atovaquone and proguanil or dihydroartemisinin against drug-resistant strains of Plasmodium falciparum

Modified fixed-ratio isobologram method for studying in vitro interactions between atovaquone and proguanil or dihydroartemisinin against drug-resistant strains of Plasmodium falciparum
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DOI:
10.1128/aac.48.11.4097-4102.2004
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发表时间:
2004-11-01
影响因子:
4.9
通讯作者:
Warhurst, DC
Warhurst, DC
中科院分区:
医学2区
文献类型:
--
作者:
Fivelman, QL;Adagu, IS;Warhurst, DC

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本文描述了一种用于研究抗疟原虫药物体外相互作用的改进的固定比率等线图方法。该方法用于检测阿托伐醌、原胍和双氢青蒿素之间的相互作用。阿托伐醌与原胍对阿托伐醌敏感菌株K1和T996具有协同作用;然而,在美拉龙(阿托伐酮和普罗胍联合用药)治疗失败后,对分离出的耐阿托伐酮菌株NGATV01失去了协同作用。阿托伐醌与dillo青蒿素对分离株NGATV01的相互作用不显著,但对阿托伐醌敏感菌株的拮抗作用不显著。讨论了体外相互作用与体内治疗的相关性。
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 dillydroartemisinin 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.