Karunajeewa Harin A, Reeder John, Lorry Kerry, Dabod Elizah, Hamzah Juliana, Page-Sharp Madhu, Chiswell Gregory M, Ilett Kenneth F, Davis Timothy M E
Medicine Unit Fremantle, School of Medicine and Pharmacology, University of Western Australia, Crawley.
Antimicrob Agents Chemother. 2006 Mar;50(3):968-74. doi: 10.1128/AAC.50.3.968-974.2006.
Drug treatment of severe malaria must be rapidly effective. Suppositories may be valuable for childhood malaria when circumstances prevent oral or parenteral therapy. We compared artesunate suppositories (n = 41; 8 to 16 mg/kg of body weight at 0 and 12 h and then daily) with intramuscular (i.m.) artemether (n = 38; 3.2 mg/kg at 0 h and then 1.6 mg/kg daily) in an open-label, randomized trial with children with severe Plasmodium falciparum malaria in Papua New Guinea (PNG). Parasite density and temperature were measured every 6 h for > or = 72 h. Primary endpoints included times to 50% and 90% parasite clearance (PCT50 and PCT90) and the time to per os status. In a subset of 29 patients, plasma levels of artemether, artesunate, and their common active metabolite dihydroartemisinin were measured during the first 12 h. One suppository-treated patient with multiple complications died within 2 h of admission, but the remaining 78 recovered uneventfully. Compared to the artemether-treated children, those receiving artesunate suppositories had a significantly earlier mean PCT50 (9.1 versus 13.8 h; P = 0.008) and PCT90 (15.6 versus 20.4 h; P = 0.011). Mean time to per os status was similar for each group. Plasma concentrations of primary drug plus active metabolite were significantly higher in the artesunate suppository group at 2 h postdose. The earlier initial fall in parasitemia with artesunate is clinically advantageous and mirrors higher initial plasma concentrations of active drug/metabolite. In severely ill children with malaria in PNG, artesunate suppositories were at least as effective as i.m. artemether and may, therefore, be useful in settings where parenteral therapy cannot be given.
重症疟疾的药物治疗必须迅速起效。当情况不允许进行口服或肠胃外治疗时，栓剂对于儿童疟疾可能很有价值。在巴布亚新几内亚（PNG）对患有严重恶性疟原虫疟疾的儿童进行的一项开放标签、随机试验中，我们将青蒿琥酯栓剂（n = 41；0小时和12小时时为8至16毫克/千克体重，然后每日一次）与肌肉注射（i.m.）蒿甲醚（n = 38；0小时时为3.2毫克/千克，然后每日1.6毫克/千克）进行了比较。在≥72小时的时间里，每6小时测量一次寄生虫密度和体温。主要终点包括达到50%和90%寄生虫清除率（PCT50和PCT90）的时间以及恢复经口进食状态的时间。在29名患者的一个亚组中，在最初12小时内测量了蒿甲醚、青蒿琥酯及其共同活性代谢物双氢青蒿素的血浆水平。一名接受栓剂治疗且有多种并发症的患者在入院后2小时内死亡，但其余78名患者顺利康复。与接受蒿甲醚治疗的儿童相比，接受青蒿琥酯栓剂治疗的儿童的平均PCT50（9.1小时对13.8小时；P = 0.008）和PCT90（15.6小时对20.4小时；P = 0.011）明显更早。每组恢复经口进食状态的平均时间相似。给药后2小时，青蒿琥酯栓剂组的主要药物加活性代谢物的血浆浓度明显更高。青蒿琥酯导致的寄生虫血症早期下降在临床上具有优势，反映出活性药物/代谢物的初始血浆浓度更高。在PNG患有重症疟疾的儿童中，青蒿琥酯栓剂至少与肌肉注射蒿甲醚一样有效，因此，在无法进行肠胃外治疗的情况下可能有用。
