In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum
In vitro activity of ferroquine (SAR97193) is independent of chloroquine resistance in Plasmodium falciparum
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DOI：
10.4269/ajtmh.2006.75.1178
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发表时间：
2006-12-01
影响因子：
3.3
通讯作者：
Mordmueller, Benjamin
中科院分区：
文献类型：
--
作者：
Kreidenweiss, Andrea;Kremsner, Peter G.;Mordmueller, Benjamin
如今，几乎所有疟疾流行地区都出现了对氯喹有抗药性的疟疾。Ferroquine是氯喹的衍生物，在体外和动物模型中显示出良好的活性，但交叉耐药性的发展令人担忧。我们测试了恶性疟原虫从加蓬现场分离物的体外亲和性，以ferroquine，氯喹，青蒿琥酯。正如预期的那样，氯喹耐药性存在于所有寄生虫分离株（中位数50%抑制浓度= 113 nmol/L）。Ferroquine（1.94 nmol/L）和青蒿琥酯（0.96 nmol/L）具有高度活性，三种药物之间均未观察到显著相关性。与我们的研究结果相反，以前的研究表明氯喹和Ferroquine活动之间存在关联。我们可以重现这种关联，通过使用不同的初始寄生虫血症，但协方差分析显示，初始寄生虫血症，而不是寄生虫菌株是氯喹和Ferroquine活动之间的相关性的关键决定因素。我们的结论是，氯喹抗性寄生虫中的氯喹是高度活跃的，我们预计没有增强选择对氯喹抗性寄生虫中的氯喹抗性。
Nowadays, chloroquine-resistant malaria appears in almost all endemic regions. Ferroquine is a derivative of chloroquine and shows good activity in vitro and in animal models, but the development of cross-resistance is of concern. We tested in vitro susceptibilities of Plasmodium falciparum field isolates from Gabon to ferroquine, chloroquine, and artesunate. As expected, chloroquine resistance was present in all parasite isolates (median 50% inhibitory concentration = 113 nmol/L). Ferroquine (1.94 nmol/L) and artesunate (0.96 nmol/L) were highly active, and no significant correlation between any of the three drugs was observed. In contrast to our findings, previous studies showed an association between chloroquine and ferroquine activities. We could reproduce this association by using different initial parasitemias, but analysis of covariance revealed that initial parasitemia and not parasite strain was the critical determinant for the correlation between chloroquine and ferroquine activities. We conclude that ferroquine is highly active in chloroquine-resistant parasites, and we anticipate no enhanced selection for resistance against ferroquine in chloroquine-resistant parasites.