Centre for Pathophysiology, Infectiology and Immunology, Institute of Specific Prophylaxis and Tropical Medicine, Medical University of Vienna, Vienna, Austria.
Wien Klin Wochenschr. 2010 Oct;122 Suppl 3:57-60. doi: 10.1007/s00508-010-1439-5.
Following the advent of mefloquine resistance in Plasmodium falciparum in Thailand in the 1990s, the combined treatment of falciparum malaria with artesunate and mefloquine was found to be highly effective in treating and curing the patients in the affected areas. Monitoring of the clinical-parasitological response and of the in vitro sensitivity of P. falciparum was systematically conducted in order to detect any signs of failure of this type of artemisinin-based combination treatment (ACT). In earlier observations the in vitro activity of artemisinin was found to be significantly enhanced when combined with retinol. The same applies to mefloquine. In order to check whether the synergism between artemisinin and mefloquine was maintained in the presence of retinol, the pharmacodynamic interaction of the three compounds was investigated in the western border area of Thailand. Successful parallel tests with mefloquine, artemisinin, retinol, mefloquine-artemisinin 5:1 as well as mefloquine-artemisinin (5:1) + retinol low, medium and high were obtained with 43 fresh parasite isolates. The retinol concentrations in the low, medium and high formulations corresponded to the 50th, 65th and 80th percentile of the physiological mean concentrations in the blood of healthy adults. The IC(50), IC(90) and IC(99) values for mefloquine alone showed a further increase over the data of 2008. In the combinations with artemisinin and retinol moderate synergism was observed at the IC(50), but synergism increased strongly at the IC(90) and the IC(99).
继 20 世纪 90 年代在泰国出现恶性疟原虫对甲氟喹的抗药性后，青蒿琥酯与甲氟喹联合治疗恶性疟被证明对治疗和治愈受影响地区的患者非常有效。为了检测这种基于青蒿素的联合治疗（ACT）是否失败，系统地监测了临床寄生虫学反应和恶性疟原虫的体外敏感性。早期观察发现，青蒿素与视黄醇联合使用时，其体外活性显著增强。甲氟喹也是如此。为了检查青蒿素和甲氟喹在视黄醇存在下的协同作用是否保持不变，在泰国西部边境地区研究了这三种化合物的药效学相互作用。用 43 个新鲜寄生虫分离株成功地进行了平行测试，包括甲氟喹、青蒿素、视黄醇、甲氟喹-青蒿素 5:1 以及甲氟喹-青蒿素（5:1）+低、中、高视黄醇。低、中、高三种配方中的视黄醇浓度分别对应于健康成年人血液中生理平均浓度的第 50、65 和 80 百分位数。单独使用甲氟喹的 IC（50）、IC（90）和 IC（99）值比 2008 年的数据进一步增加。在与青蒿素和视黄醇的组合中，在 IC（50）处观察到适度协同作用，但在 IC（90）和 IC（99）处协同作用显著增强。
