Pirker-Krassnig Daniela K, Wernsdorfer Gunther, Sirichaisinthop Jeeraphat, Rojanawatsirivet Chaiporn, Kollaritsch Herwig, Wernsdorfer Walther H
Division of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria.
Wien Klin Wochenschr. 2004;116 Suppl 4:47-52.
The occurrence of chloroquine resistance in Plasmodium vivax underlines the need for monitoring the drug response of this important malaria parasite and for the evaluation of alternative therapeutic agents. In-vitro methods facilitate these tasks. This investigation employed a recently developed in-vitro micro-technique and validated it for lumefantrine and desbutyl-benflumetol, a compound that was initially considered a metabolite of lumefantrine. The studies were conducted in 2001 at Mae Sot, a town situated in northwestern Thailand near the border to Myanmar. Parallel in-vitro tests with lumefantrine and desbutyl-benflumetol were carried out with 53 fresh isolates of P. vivax. For both compounds, the parasite showed a homogenous, log-normal inhibition pattern with nearly parallel log-probit regressions. The geometric mean drug concentrations effecting complete growth inhibition were 2361 nM for lumefantrine and 187 nM for desbutyl-benflumetol. With p=3.264 x 10(-18) the difference was highly significant. The EC50 and EC90 values for lumefantrine, 17.6 nM and 448.5 nM, respectively, were much higher as compared to those determined for desbutyl-benflumetol, with 1.5 nM and 39.7 nM. This difference expressed itself in a highly significant Power Ratio (PR) of 11.0. The activity of desbutyl-benflumetol in P. vivax exceeds that of lumefantrine by one order of magnitude, suggesting a high, hitherto unexploited therapeutic potential of desbutyl-benflumetol.
间日疟原虫对氯喹产生耐药性，这突出表明有必要监测这种重要疟原虫的药物反应，并评估替代治疗药物。体外方法有助于完成这些任务。本研究采用了一种最近开发的体外微技术，并对卤泛群和去丁基苯芴醇（最初被认为是卤泛群的一种代谢产物）进行了验证。这些研究于2001年在泰国西北部靠近缅甸边境的美索镇进行。用53株新鲜的间日疟原虫分离株对卤泛群和去丁基苯芴醇进行了平行体外试验。对于这两种化合物，疟原虫均呈现出均匀的对数正态抑制模式，对数概率回归近乎平行。实现完全生长抑制的几何平均药物浓度，卤泛群为2361 nM，去丁基苯芴醇为187 nM。p值为3.264×10⁻¹⁸，差异极为显著。卤泛群的EC50和EC90值分别为17.6 nM和448.5 nM，与去丁基苯芴醇的1.5 nM和39.7 nM相比要高得多。这种差异表现为高达11.0的显著效力比（PR）。去丁基苯芴醇对间日疟原虫的活性比卤泛群高出一个数量级，表明去丁基苯芴醇具有很高的、迄今尚未开发的治疗潜力。
