In vitro interaction of lumefantrine and piperaquine by atorvastatin against Plasmodium falciparum.
In vitro interaction of lumefantrine and piperaquine by atorvastatin against Plasmodium falciparum.
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DOI：
10.1186/1475-2875-13-189
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发表时间：
2014-05-25
期刊：
影响因子：
3
通讯作者：
Pradines B
中科院分区：
文献类型：
--
作者：
Dormoi J;Savini H;Amalvict R;Baret E;Pradines B
迫切需要发现新的抗疟疾药物和联合治疗。组合方法保护每种药物不产生耐药性，并普遍降低疟疾的总体传播率。他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶的抑制剂，是一类具有体外抗疟作用的降脂药物，阿托伐他汀的作用尤为突出。然而，阿托伐他汀的消除半衰期短（14小时），有效的抗疟疾药物组合必须将消除半衰期短的药物和消除半衰期长的药物相结合。目前工作的目的是在具有长消除半衰期的标准新型抗疟疾药物（如本芴醇、哌喹、咯萘啶和阿托伐醌）中确定新的潜在合作伙伴，以提高阿托伐他汀对不同恶性疟原虫株的体外活性，从而治疗无并发症的疟疾。采用同位素法研究了阿托伐他汀与本芴醇、哌喹、咯萘啶和阿托伐醌联合用药对13株恶性疟原虫的体外相互作用。阿托伐他汀与咯萘啶、哌喹和本芴醇具有相加效应。阿托伐他汀在临床观察中预期的浓度下增加了本芴醇和哌喹的体外活性。与1 μM阿托伐他汀联合用药时，本芴醇的平均IC 50值从31.9 nM显著降低至20.5 nM（降低35.7%）。尽管体外数据表明阿托伐他汀改善了本芴醇和哌喹的活性，但在体内不一定如此。喹诺喹是一种具有长终末消除半衰期的新药，是目前很有前途的抗疟药物。
There is an urgent need for the discovery of new anti-malarial drugs and combination therapy. A combinatorial approach protects each drug from the development of resistance and reduces generally the overall transmission rate of malaria. Statins, the inhibitors of 3-hydroxy-3-methylglutaryl-Coenzyme A reductase and a family of lipid-lowering drugs, have in vitro anti-malarial properties, and more specially atorvastatin. However, atorvastatin has a short elimination half-life (14 hours) and an efficient combination of anti-malarial drugs must associate a drug with a short elimination half-life and a drug with a long elimination half-life. The objective of the present work was to identify new potential partners among standard new anti-malarial drugs with long elimination half-life, such as lumefantrine, piperaquine, pyronaridine and atovaquone, to improve the in vitro activity of atorvastatin against different Plasmodium falciparum strains to treat uncomplicated malaria. In vitro interaction of atorvastatin in combination with lumefantrine, piperaquine, pyronaridine and atovaquone was assessed against 13 P. falciparum strains by isotopic test. Atorvastatin showed additive effects with pyronaridine, piperaquine and lumefantrine. Atorvastatin increased the in vitro activity of lumefantrine and piperaquine at concentrations expected in clinical observations. The average IC50 values of lumefantrine decreased significantly from 31.9 nM to 20.5 nM (a decrease of 35.7%) in combination with 1 μM of atorvastatin. Even though in vitro data indicate that atorvastatin improved the activity of lumefantrine and piperaquine, the same may not necessarily be true in vivo. Piperaquine, a new drug with long terminal elimination half-life, is currently a very promising anti-malarial drug.
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影响因子：
3
作者：
Lim P;Alker AP;Khim N;Shah NK;Incardona S;Doung S;Yi P;Bouth DM;Bouchier C;Puijalon OM;Meshnick SR;Wongsrichanalai C;Fandeur T;Le Bras J;Ringwald P;Ariey F
通讯作者：
Ariey F
影响因子：
2.3
作者：
Henry, Maud;Alibert, Sandrine;Pradines, Bruno
通讯作者：
Pradines, Bruno
影响因子：
3
作者：
Dormoi, Jerome;Briolant, Sebastien;Pradines, Bruno
通讯作者：
Pradines, Bruno
影响因子：
4.9
作者：
Dokomajilar, C;Nsobya, SL;Dorsey, G
通讯作者：
Dorsey, G
中缅边境恶性疟原虫对哌喹的体外敏感性及其与候选基因多态性的关联
影响因子：
4.9
作者：
Hao, Mingming;Jia, Dandan;Cui, Liwang
通讯作者：
Cui, Liwang