Basco L K, Ramiliarisoa O, Le Bras J
Centre National de Reference de la Chimiosensibilite du Paludisme, Laboratoire de Parasitologie, Hopital Bichat-Claude Bernard, Paris, France.
Am J Trop Med Hyg. 1995 Oct;53(4):388-91. doi: 10.4269/ajtmh.1995.53.388.
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 were 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.
使用同位素半微量药物敏感性试验，评估了阿托伐醌（566C80）的体外活性，并将其与氯喹、奎宁、甲氟喹、卤泛群、蒿甲醚、乙胺嘧啶和环氯胍针对恶性疟原虫非洲分离株和克隆的活性进行了比较。阿托伐醌对氯喹敏感的L-3克隆（几何平均50%抑制浓度[IC50]=0.978 nM）和L-16克隆（平均IC50=0.680 nM）以及对多药耐药的FCM 29克隆（平均IC50=1.76 nM）具有高活性。针对氯喹敏感分离株（n=35；几何平均IC50=0.889 nM）和氯喹耐药寄生虫（n=26；几何平均IC50=0.906 nM），观察到阿托伐醌的IC50值同样较低。阿托伐醌与其他抗疟药物之间的体外反应不相关，表明不存在体外交叉耐药性。阿托伐醌具有高体外活性，且在体外没有任何与其他抗疟药物产生交叉耐药性的证据，这是有利于该药物进一步开发用于临床的一个因素。
