Division of Parasitology, Central Drug Research Institute, Lucknow, India.
Chemotherapy. 2010;56(3):178-83. doi: 10.1159/000315066. Epub 2010 May 21.
alpha/beta arteether (AE), an effective artemisinin derivative, was developed as intramuscular injection for multidrug-resistant (MDR) and severe falciparum malaria, but intramuscular treatment has its own limitations and cannot be given to patients in rural areas where proper hospital facilities are not available and people are reluctant to take injections. Due to widespread occurrence of MDR strains of Plasmodiumfalciparum, an oral AE formulation is urgently needed to cure the malaria patients.
Several AE formulations were prepared and tested orally in Swiss mice infected with MDR P. yoelii nigeriensis at a dose of 50 mg/kg/day for 5 days. The comparative antimalarial efficacy of eight different AE formulations was assessed at different time intervals in treated and control animals.
Three new AE formulations, namely AE F-2, F-10B and F-14, were found to have 100% curative antimalarial activity in an experimental model, as shown by survival of treated animals beyond 28 days, with no recrudescence of parasitemia being recorded. Another two formulations, AE F-8 and F-9B, produced 96-97% cure.
Five alpha/beta AE formulations (F-2, F-10B, F-8, F-9B and F-14) can be considered potential candidates for further drug development. AE F-14, a solid dosage form of AE prepared by completely removing oil and incorporating 0.2% cholesterol, is a new promising lead, even in pediatric malaria, which can reduce the neurotoxic potential of AE and other artemisinin derivatives.
alpha/beta 青蒿琥酯（AE）是一种有效的青蒿素衍生物，开发为肌肉注射制剂，用于治疗耐多药（MDR）和重症恶性疟，但肌肉注射有其自身的局限性，无法在没有适当医院设施且人们不愿意接受注射的农村地区使用。由于恶性疟原虫 MDR 株的广泛发生，迫切需要一种口服 AE 制剂来治疗疟疾患者。
制备了几种 AE 制剂，并以 50mg/kg/天的剂量每天口服 5 天，在感染 MDR 约氏疟原虫尼日利亚株的瑞士小鼠中进行了测试。在不同时间间隔，用治疗和对照动物评估了 8 种不同 AE 制剂的比较抗疟疗效。
发现三种新的 AE 制剂，即 AE F-2、F-10B 和 F-14，在实验模型中具有 100%的治愈性抗疟活性，表现为治疗动物的存活率超过 28 天，未记录到寄生虫血症的复发。另外两种制剂，AE F-8 和 F-9B，产生了 96-97%的治愈率。
五种 alpha/beta AE 制剂（F-2、F-10B、F-8、F-9B 和 F-14）可被视为进一步药物开发的潜在候选药物。AE F-14 是一种通过完全去除油并加入 0.2%胆固醇制备的 AE 固体剂型，是一种很有前途的新先导化合物，甚至在儿科疟疾中也有应用前景，它可以降低 AE 和其他青蒿素衍生物的神经毒性。
