Kyle D E, Teja-Isavadharm P, Li Q, Leo K
Department of Parasitology, Walter Reed Army Institute of Research, Washington DC, USA.
Med Trop (Mars). 1998;58(3 Suppl):38-44.
The critical decisions of which artemisinin derivative(s) to use and by which route(s) of administration for falciparum malaria are complex scientifically and politically. Despite the need for additional pharmacokinetic, pharmacodynamic and toxicokinetic data, these drugs are too important to delay concise, rational recommendations any longer. These types of decisions must be made now, implemented on a multinational level with WHO leadership, and revised as new findings emerge. For acute, uncomplicated disease, per os dosing of artesunate or artemether for three days is recommended, but only in combination with other antimalarial drugs like mefloquine. For severe falciparum malaria, intravenous administration is the preferred route, yet current formulations for intravenous dosing are not optimal and should be an area for future development emphasis. Clearly intramuscular administration of artemether has proven effective for severe disease, yet dosing regimens shouldn't be designed with ultimate parasitological cure as the aim and the problem of bioavailability of the sesame oil formulations must be examined further. Once the life-saving reduction in parasitemia and pathophysiological sequelae have been achieved, the patient can be given oral medication to affect radical cure. Much more data will be required to define the role of per rectum dosing for the treatment of severe malaria, yet this approach holds great promise as a life-saving intervention in rural areas where this disease has it most dramatic impact.
对于恶性疟使用哪种青蒿素衍生物以及通过何种给药途径进行治疗，这一关键决策在科学和政治层面都很复杂。尽管还需要更多的药代动力学、药效动力学和毒代动力学数据，但这些药物非常重要，不能再延迟给出简洁、合理的建议了。现在必须做出这类决策，在世卫组织的领导下在多国层面实施，并随着新发现的出现进行修订。对于急性非复杂性疾病，建议口服青蒿琥酯或蒿甲醚三天，但要与甲氟喹等其他抗疟药物联合使用。对于严重恶性疟，静脉给药是首选途径，但目前的静脉给药制剂并非最佳，应作为未来重点发展领域。显然，蒿甲醚肌肉注射已被证明对严重疾病有效，但给药方案不应以最终的寄生虫学治愈为目标，芝麻油制剂的生物利用度问题必须进一步研究。一旦实现了寄生虫血症和病理生理后遗症的挽救生命的降低，就可以给患者口服药物以实现根治。还需要更多数据来确定直肠给药在治疗严重疟疾中的作用，但这种方法作为一种在该疾病影响最为严重的农村地区的挽救生命的干预措施，具有很大的前景。
