Barata Lídia, Houzé Pascal, Boutbibe Khadija, Zanghi Gigliola, Franetich Jean-François, Mazier Dominique, Clain Jérôme
Sorbonne Universités, Université Pierre et Marie Curie, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France UMR 216, Faculté de Pharmacie, Université Paris Descartes, Université Sorbonne Paris Cité, Paris, France UMR 216, Institut de Recherche pour le Développement, Paris, France.
Laboratoire de Biochimie, Secteur Chromatographie, Hôpital Saint Louis, AP-HP, Paris, France.
Antimicrob Agents Chemother. 2016 Jun 20;60(7):4333-5. doi: 10.1128/AAC.01685-15. Print 2016 Jul.
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.
阿托伐醌与氯胍之间的相互作用从未针对肝期疟疾进行过研究，而肝期疟疾是该药物组合用于化学预防时的主要靶点。我们使用缺乏细胞色素P450活性的人肝细胞，从而避免氯胍代谢为强效环氯胍，体外实验表明阿托伐醌-氯胍组合可协同抑制啮齿动物约氏疟原虫的生长。这些结果为阿托伐醌-氯胍用于疟疾化学预防的高效性提供了药理学依据。
