In vitro stage-specific sensitivity of Plasmodium falciparum to quinine and artemisinin drugs
In vitro stage-specific sensitivity of Plasmodium falciparum to quinine and artemisinin drugs
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DOI：
10.1016/0020-7519(96)89380-5
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发表时间：
1996-05-01
影响因子：
4
通讯作者：
Davis, TME
中科院分区：
文献类型：
--
作者：
Skinner, TS;Manning, LS;Davis, TME
用体外法测定了奎宁、氯喹和青蒿素、蒿甲醚、青蒿琥酯、双氢青蒿素4种青蒿素药物对4株恶性疟原虫适应株和2株标准株的抑制作用。所有分离株均对广泛使用的抗疟药奎宁（EC（50）范围为3 × 10（-8）-1 × 10（-7）mol/L）和氯喹（EC（50）范围为1 × 10（-9）-7 × 10（-9）mol/L）敏感，无论患者的地理来源或治疗史如何。青蒿素类药物的EC（50）值为3 × 10（-11）~ 3 × 10（-8）mol/L。阶段特异性数据表明，奎宁对成熟寄生虫形式具有主要作用模式，在药物暴露2-4小时内实现80-100%的生长抑制。青蒿素、蒿甲醚和双氢青蒿素3种青蒿素类药物的阶段特异性活性与奎宁不同，且每种衍生物均显示出独特的阶段特异性特征。青蒿素对环和棘突都迅速有效，在6-8小时内达到100%的生长抑制。蒿甲醚的抑制作用不太迅速，需要10小时才能达到70-80%的环期生长抑制。双氢青蒿素对所有阶段的寄生虫都非常有效，在大多数情况下，在接触后2-4小时内达到100%的生长抑制。结果证实青蒿素药物是有效的抗疟药物，并表明与常规抗疟药物相比，不同的阶段特异性特征。版权所有（C）1996澳大利亚寄生虫学会。出版社：Elsevier Science Ltd
The inhibitory effects of quinine, chloroquine and 4 qinghaosu drugs, artemisinin, artemether, artesunate and dihydroartemisinin, on 4 culture-adapted isolates and 2 standard clones of Plasmodium falciparum were determined in vitro. All isolates were sensitive to the widely used antimalarial drugs quinine (EC(50) range 3 x 10(-8)-1 x 10(-7) mol/L) and chloroquine (EC(50) range 1 x 10(-9)-7 x 10(-9) mol/L), irrespective of the geographical origin or treatment history of the patients from which they were taken. In general, the qinghaosu drugs were more potent than the conventional antimalarials, having EC(50) values of 3 x 10(-11)-3 x 10(-8) mol/L. Stage-specific data indicated that quinine has a primary mode of action on mature parasite forms, achieving 80-100% growth inhibition within 2-4 h of drug exposure. The stage-specific activity of the 3 qinghaosu drugs artemisinin, artemether and dihydroartemisinin differed from that of quinine, and each derivative displayed a unique stage-specific profile. Artemisinin was rapidly effective against both rings and schizonts, achieving 100% growth inhibition within 6-8 h. The inhibitory effects of artemether were less rapid, requiring 10 h to achieve 70-80% ring stage growth inhibition. Dihydroartemisinin was highly effective against all parasite stages, in most cases achieving 100% growth inhibition within 2-4 h of exposure. The results confirm that the qinghaosu drugs are potent antimalarials, and suggest different stage-specific profiles compared to conventional antimalarial drugs. Copyright (C) 1996 Australian Society for Parasitology. Published by Elsevier Science Ltd.