Halpaap B, Ndjave M, Paris M, Benakis A, Kremsner P G
Department of Pharmacology, University Medical Centre, Geneva, Switzerland.
Am J Trop Med Hyg. 1998 Mar;58(3):365-8. doi: 10.4269/ajtmh.1998.58.365.
A thermostable suppository of artesunate (artesunic acid) has been developed. In Gabon, 12 children with Plasmodium falciparum malaria received two administrations of this suppository in a 4-hr interval. Parasitemia and fever were then measured and the plasma levels of artesunate and its active metabolite, dihydroartemisinin, were determined by means of a reversed phase high-pressure liquid chromatography method using reductive electrochemical detection. Substantial parasite clearance (97-100%) was noted 24 hr after the beginning of the treatment and body temperature had returned to normal. Absorption, metabolism, and elimination of artesunate were rapid. Mean values of maximum plasma levels (Cmax) and maximum concentration peak times (tmax) were evaluated. The Cmax of dihydroartemisinin (0.18 +/- 0.10 microg/ml [mean +/- SE]) was higher than the Cmax of artesunate (0.09 +/- 0.04 microg/ml) and the tmax of dihydroartemisinin (1.13 +/- 0.58 hr) was higher than the tmax of artesunate (0.58 +/- 0.19 hr). Plasma levels 30 min after the second suppository administration were not consistently higher than those found 30 min after the first administration.
已研制出一种青蒿琥酯（青蒿素酸）的热稳定栓剂。在加蓬，12名患恶性疟原虫疟疾的儿童在4小时间隔内接受了两次这种栓剂给药。随后测量了疟原虫血症和发热情况，并采用还原电化学检测的反相高压液相色谱法测定了青蒿琥酯及其活性代谢物双氢青蒿素的血浆水平。治疗开始24小时后观察到疟原虫大量清除（97 - 100%），体温恢复正常。青蒿琥酯的吸收、代谢和消除迅速。评估了最大血浆水平（Cmax）和最大浓度峰值时间（tmax）的平均值。双氢青蒿素的Cmax（0.18±0.10微克/毫升[平均值±标准误]）高于青蒿琥酯的Cmax（0.09±0.04微克/毫升），双氢青蒿素的tmax（1.13±0.58小时）高于青蒿琥酯的tmax（0.58±0.19小时）。第二次栓剂给药后30分钟的血浆水平并不始终高于第一次给药后30分钟的水平。
