Basco L K, Le Bras J
Centre National de Reference pour la Chimiosensibilite du Paludisme, Hopital Bichat-Claude Bernard, Paris, France.
Am J Trop Med Hyg. 1993 Sep;49(3):301-7. doi: 10.4269/ajtmh.1993.49.301.
The in vitro activities of chloroquine, quinine, mefloquine, halofantrine, artemisinin, arteether, artemether, and artelinate were evaluated against African clones and isolates of Plasmodium falciparum, using an isotopic, semimicro, drug susceptibility test. The chloroquine-resistant FCM 29 clone was 1.6 and 6.2 times more susceptible to artemisinin when compared with the chloroquine-susceptible, mefloquine-, and halofantrine-resistant L-3 and L-16 clones, respectively. Cross-resistance patterns between the standard antimalarial drugs and artemisinin were determined against 36 African isolates of P. falciparum obtained from imported cases of malaria in France. Chloroquine-resistant isolates (n = 21) were significantly more susceptible to artemisinin (50% inhibitory concentration [IC50] 7.67 nM), arteether (IC50 3.88 nM), artemether (IC50 3.71 nM), and artelinate (IC50 3.46 nM), as compared with the 15 chloroquine-susceptible isolates (IC50 11.4, 5.66, 5.14, and 5.04 nM, respectively). Arteether, artemether, and artelinate were equally effective and twice as potent as artemisinin. A significant positive correlation was found between artemisinin and mefloquine (r = 0.424, P = 0.022), artemisinin and halofantrine (r = 0.569, P < 0.001), chloroquine and quinine (r = 0.651, P < 0.001), and mefloquine and halofantrine (r = 0.863, P < 0.001), suggesting in vitro cross-resistance among these drugs. The present in vitro findings require confirmation in clinical studies.
采用同位素半微量药物敏感性试验，评估了氯喹、奎宁、甲氟喹、卤泛群、青蒿素、蒿乙醚、蒿甲醚和青蒿琥酯对恶性疟原虫非洲克隆株和分离株的体外活性。与氯喹敏感、甲氟喹和卤泛群耐药的L-3和L-16克隆株相比，氯喹耐药的FCM 29克隆株对青蒿素的敏感性分别高1.6倍和6.2倍。针对从法国输入性疟疾病例中获得的36株非洲恶性疟原虫分离株，确定了标准抗疟药物与青蒿素之间的交叉耐药模式。与15株氯喹敏感分离株（IC50分别为11.4、5.66、5.14和5.04 nM）相比，氯喹耐药分离株（n = 21）对青蒿素（50%抑制浓度[IC50] 7.67 nM）、蒿乙醚（IC50 3.88 nM）、蒿甲醚（IC50 3.71 nM）和青蒿琥酯（IC50 3.46 nM）的敏感性明显更高。蒿乙醚、蒿甲醚和青蒿琥酯同样有效，效力是青蒿素的两倍。青蒿素与甲氟喹（r = 0.424，P = 0.022）、青蒿素与卤泛群（r = 0.569，P < 0.001）、氯喹与奎宁（r = 0.651，P < 0.001）以及甲氟喹与卤泛群（r = 0.863，P < 0.001）之间存在显著正相关，表明这些药物之间存在体外交叉耐药性。目前的体外研究结果需要在临床研究中得到证实。
