IN-VITRO ACTIVITY OF ATOVAQUONE AGAINST THE AFRICAN ISOLATES AND CLONES OF PLASMODIUM-FALCIPARUM
IN-VITRO ACTIVITY OF ATOVAQUONE AGAINST THE AFRICAN ISOLATES AND CLONES OF PLASMODIUM-FALCIPARUM
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DOI：
10.4269/ajtmh.1995.53.388
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发表时间：
1995-10-01
影响因子：
3.3
通讯作者：
LEBRAS, J
中科院分区：
文献类型：
--
作者：
BASCO, LK;RAMILIARISOA, O;LEBRAS, J
使用同位素半微量药敏试验评估了阿托伐醌 (566C80) 的体外活性，并与氯喹、奎宁、甲氟喹、卤泛群、蒿甲醚、乙胺嘧啶和环胍对非洲恶性疟原虫分离株和克隆的体外活性进行了比较。阿托伐醌对氯喹敏感的 L-3（几何平均 50% 抑制浓度 [IC50] = 0.978 nM）和 L-16 克隆（平均 IC50 = 0.680 nM）以及多重耐药 FCM 29 克隆（平均 IC50 = 1.76 nM）具有高度活性。对于氯喹敏感分离株（n = 35；几何平均值 IC50 = 0.889 nM）和氯喹抗性寄生虫（n = 26；几何平均值 IC50 = 0.906 nM），观察到阿托伐醌的类似低 IC50 值。阿托伐醌和其他抗疟药之间的体外反应不相关，表明不存在体外交叉耐药性。阿托伐醌的高体外活性，没有任何体外证据表明与其他抗疟药物对天然存在的疟疾寄生虫存在交叉耐药性，这是有利于该药物进一步开发用于临床的一个因素。
The in vitro activity of atovaquone (566C80) was evaluated and compared with that of chloroquine, quinine, mefloquine, halofantrine, artemether, pyrimethamine, and cycloguanil against African isolates and clones of Plasmodium falciparum using an isotopic, semimicro, drug susceptibility test. Atovaquone was highly active against the chloroquine-susceptible L-3 (geometric mean 50% inhibitory concentration [IC50] = 0.978 nM) and L-16 clones (mean IC50 = 0.680 nM) and against the multidrug-resistant FCM 29 clone (mean IC50 = 1.76 nM). Similar low IC50 values for atovaquone w ere observed against the chloroquine-susceptible isolates (n = 35; geometric mean IC50 = 0.889 nM) and the chloroquine-resistant parasites (n = 26; geometric mean IC50 = 0.906 nM). The in vitro responses between atovaquone and the other antimalarial drugs were not correlated, indicating the absence of in vitro cross-resistance. The high in vitro activity of atovaquone without any in vitro evidence for cross-resistance with other antimalarial drugs against the naturally occurring malaria parasites is a factor that favors further development of the drug for clinical use.