Institute of Specific Prophylaxis and Tropical Medicine, Centre for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
Wien Klin Wochenschr. 2009 Oct;121 Suppl 3:27-31. doi: 10.1007/s00508-009-1231-6.
Mefloquine, a 4-quinolinemethanol derivative, was introduced in Thailand after Plasmodium falciparum had acquired almost universal resistance to the 4-aminoquinolines and antifols. However, also resistance to mefloquine has become an increasing problem, but artemisinin-based combination therapy (ACT) with mefloquine and artesunate remained until recently sufficiently effective. Since synergistic interaction between quinine, another 4-quinolinemethanol, with retinol was observed earlier, the investigations were expanded to mefloquine. The interaction between mefloquine and retinol at concentrations equal to the 50(th), 65(th) and 80(th) percentile of the physiological retinol levels in healthy adults was determined in 37 fresh isolates of P. falciparum. The mean IC(50), IC(90) and IC(99) values for mefloquine were 1.76, 9.81 and 39.78 microM, those for mefloquine + retinol "low" 0.33, 1.37 and 4.33 microM, those for mefloquine + retinol "medium" 0.29, 1.15 and 3.48 microM, and those for mefloquine + retinol "high" 0.20, 0.85 and 2.70 microM. Evidence for strong synergism between mefloquine and retinol in P. falciparum was highly significant.
盐酸甲氟喹，4-喹啉甲醇衍生物，在恶性疟原虫对 4-氨基喹啉和抗叶酸类药物几乎普遍产生耐药性之后，在泰国被引进。然而，对盐酸甲氟喹的耐药性也成为日益严重的问题，但青蒿素为基础的联合疗法（ACT）加用盐酸甲氟喹和青蒿琥酯在最近仍保持着相当的疗效。由于以前已经观察到 4-喹啉甲醇奎宁与视黄醇之间的协同相互作用，所以对盐酸甲氟喹也进行了相应的研究。在 37 株新鲜分离的恶性疟原虫中，测定了浓度分别等于健康成年人生理视黄醇水平第 50、65 和 80 百分位数的盐酸甲氟喹与视黄醇之间的相互作用。盐酸甲氟喹的平均 IC50、IC90 和 IC99 值分别为 1.76、9.81 和 39.78 microM，盐酸甲氟喹+视黄醇“低”浓度的分别为 0.33、1.37 和 4.33 microM，盐酸甲氟喹+视黄醇“中”浓度的分别为 0.29、1.15 和 3.48 microM，盐酸甲氟喹+视黄醇“高”浓度的分别为 0.20、0.85 和 2.70 microM。这些数据表明盐酸甲氟喹与视黄醇之间存在很强的协同作用。
