Davis Timothy M E, Karunajeewa Harin A, Ilett Kenneth F
Medicine Unit, School of Medicine and Pharmacology, Fremantle Hospital, University of Western Australia, Fremantle, WA.
Med J Aust. 2005 Feb 21;182(4):181-5. doi: 10.5694/j.1326-5377.2005.tb06650.x.
There has been a relentless increase in resistance of malaria parasites to conventional antimalarial drugs, including chloroquine, sulfadoxine-pyrimethamine and mefloquine. In response to this situation, short-course artemisinin-based combination therapies (ACTs) have been developed. The World Health Organization has endorsed ACT as first-line treatment where the potentially life-threatening parasite Plasmodium falciparum is the predominant infecting species. ACTs combine the rapid schizontocidal activity of an artemisinin derivative (artesunate, artemether or dihydroartemisinin) with a longer-half-life partner drug. Although the use of chloroquine and sulfadoxine-pyrimethamine as partners in ACT improves their efficacy, this may only have value as a short-term measure in patients with a degree of immunity to malaria. Alternative currently available partner drugs include mefloquine, lumefantrine and piperaquine. Artesunate-mefloquine is highly effective but is expensive and side effects (mainly neurotoxicity) can be problematic. Artemether-lumefantrine, the only ACT available in Australia, appears less effective than artesunate-mefloquine and needs to be administered with food to ensure adequate bioavailability. Dihydroartemisinin-piperaquine is highly effective, well tolerated and relatively inexpensive. The goal of potent, safe, easy-to-administer and inexpensive ACTs may see trioxolanes in place of artemisinin derivatives, as well as novel partner drugs such as pyronaridine or naphthoquine, in the future.
疟原虫对包括氯喹、周效磺胺-乙胺嘧啶和甲氟喹在内的传统抗疟药物的耐药性一直在持续增加。针对这种情况，已研发出基于青蒿素的短疗程联合疗法（ACTs）。世界卫生组织已认可ACT作为一线治疗方法，用于以潜在危及生命的恶性疟原虫为主要感染种类的情况。ACT将青蒿素衍生物（青蒿琥酯、蒿甲醚或双氢青蒿素）的快速杀裂殖体活性与半衰期较长的辅助药物相结合。尽管在ACT中使用氯喹和周效磺胺-乙胺嘧啶作为辅助药物可提高其疗效，但这对于对疟疾有一定免疫力的患者而言可能仅具有短期价值。目前可用的替代辅助药物包括甲氟喹、本芴醇和哌喹。青蒿琥酯-甲氟喹非常有效，但价格昂贵，且副作用（主要是神经毒性）可能会成为问题。蒿甲醚-本芴醇是澳大利亚唯一可用的ACT，其疗效似乎不如青蒿琥酯-甲氟喹，且需要与食物一起服用以确保足够的生物利用度。双氢青蒿素-哌喹非常有效，耐受性良好且相对便宜。强效、安全、易于给药且价格低廉的ACT的目标可能会使三氧烷取代青蒿素衍生物，以及使咯萘啶或萘喹等新型辅助药物在未来得以应用。
