Nduati Eunice Wambui, Kamau Edward Mberu
Kenya Medical Research Institute/Wellcome Trust Collaborative Research Program, Wellcome Trust Research Laboratories, Nairobi, Kenya.
Acta Trop. 2006 Mar;97(3):357-63. doi: 10.1016/j.actatropica.2006.01.005. Epub 2006 Feb 2.
The use of synergistic drug combinations for the treatment of drug-resistant malaria is a major strategy to slow the selection and spread of Plasmodium falciparum resistant strains. In order to investigate synergistic compounds, with different modes of action, as alternative candidates for combination therapy, we used standard in vitro P. falciparum cultures and an established synergy testing method to define interactions among dapsone (DDS), atovaquone (ATQ), chlorproguanil (CPG) and its triazine metabolite chlorcycloguanil (CCG). Strong synergy was observed in the combinations DDS/CCG and ATQ/CPG. Multiple combination of these drugs, DDS/CCG/CPG/ATQ also exhibited high synergy although not higher than that of either of the two drug combinations separately. The use of this triple combination DDS/CPG/ATQ, even without an increase in synergy over their double combinations, ATQ/CPG and DDS/CCG, would contribute towards slowing the selection pressure since these drugs act against different targets and would delay the selection of parasites resistant to the three drugs, extending the useful therapeutic life of these valuable compounds.
使用协同药物组合治疗耐药性疟疾是减缓恶性疟原虫耐药菌株的选择和传播的一项主要策略。为了研究具有不同作用方式的协同化合物作为联合疗法的替代候选药物，我们使用标准的体外恶性疟原虫培养物和一种既定的协同测试方法来确定氨苯砜（DDS）、阿托伐醌（ATQ）、氯胍（CPG）及其三嗪代谢物氯环胍（CCG）之间的相互作用。在DDS/CCG和ATQ/CPG组合中观察到强烈的协同作用。这些药物的多种组合，即DDS/CCG/CPG/ATQ也表现出高度协同作用，尽管并不高于两种药物组合中任何一种单独的协同作用。使用这种三联组合DDS/CPG/ATQ，即使其协同作用没有比其双重组合ATQ/CPG和DDS/CCG有所增加，也将有助于减缓选择压力，因为这些药物作用于不同靶点，并且会延迟对这三种药物耐药的寄生虫的选择，从而延长这些有价值化合物的有效治疗寿命。
