Fernex M, Jaquet C, Mittelholzer M L, Reber R, Stürchler D
Hoffmann-La Roche AG, Pharma Klinische Forschung, Basel.
Schweiz Rundsch Med Prax. 1991 Jan 22;80(4):67-71.
The occurrence in the early 60's of stable resistance to chloroquine among Plasmodium falciparum strains in the Amazonas and on the Thai-Cambodian border has been a shock for all malariologists. This led to the search for new antimalarials without cross resistance with chloroquine. For each new drug, one of the major concerns was to define how rapidly parasites would develop resistance to this compound. Drug combinations were taken into consideration so as to achieve a delay in the appearance of resistance. The decision to test a triple combination has led to the development of Fansimef, a fixed combination with tablets containing 250 mg mefloquine, 500 mg sulfadoxine and 25 mg pyrimethamine. A very relevant delay in the development of resistance was found both in-vivo--in the P. berghei model--and in-vitro using P. falciparum. Fansimef has also been under investigations for malaria. Controlled clinical trials were performed in Africa, South America and South East Asia. The documentation for this new indication will be submitted to registration authorities in 1991. A preference alternative to continuous chemoprophylaxis is stand-by malaria treatment for travellers to regions where the malaria risk is relatively low. Stand-by treatment is under investigations in France and in Switzerland. In the search for alternative remedies against drug resistant P. falciparum malaria our attention was directed to Yingzhaosu, a new sesquiterpene peroxide of plant origin from traditional Chinese medicine. A short and convenient synthesis of this ring system gave access to a variety of structural analogues of Yingzhaosu.(ABSTRACT TRUNCATED AT 250 WORDS)
20世纪60年代初，亚马逊地区和泰柬边境的恶性疟原虫菌株出现了对氯喹的稳定耐药性，这让所有疟疾学家大为震惊。这促使人们寻找与氯喹无交叉耐药性的新型抗疟药。对于每一种新药，一个主要担忧是确定寄生虫对该化合物产生耐药性的速度有多快。人们考虑使用药物组合来延缓耐药性的出现。测试三联组合的决定促成了Fansimef的研发，它是一种固定组合片剂，含有250毫克甲氟喹、500毫克磺胺多辛和25毫克乙胺嘧啶。在体内（伯氏疟原虫模型）和体外（使用恶性疟原虫）都发现耐药性发展出现了显著延迟。Fansimef也一直在进行疟疾方面的研究。在非洲、南美洲和东南亚开展了对照临床试验。这一新适应症的相关资料将于1991年提交给注册机构。对于前往疟疾风险相对较低地区的旅行者，备用疟疾治疗是持续化学预防的一个更好选择。法国和瑞士正在对备用治疗进行研究。在寻找针对耐药性恶性疟原虫疟疾的替代疗法时，我们将注意力转向了青蒿素，一种源自传统中药的新型倍半萜过氧化物。对这个环系进行简短而简便的合成，可得到多种青蒿素的结构类似物。（摘要截取自250词）
