Newton P, Suputtamongkol Y, Teja-Isavadharm P, Pukrittayakamee S, Navaratnam V, Bates I, White N
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Antimicrob Agents Chemother. 2000 Apr;44(4):972-7. doi: 10.1128/AAC.44.4.972-977.2000.
The pharmacokinetic properties of oral and intravenous artesunate (2 mg/kg of body weight) were studied in 19 adult patients with acute uncomplicated Plasmodium falciparum malaria by using a randomized crossover design. A sensitive bioassay was used to measure the antimalarial activity in plasma which results from artesunate and its principal metabolite, dihydroartemisinin. The oral study was repeated with 15 patients during convalescence. The mean absolute oral bioavailability of the antimalarial agent in patients with acute malaria was 61% (95% confidence interval [CI], 52 to 70%). The absorption and elimination of oral artesunate were rapid, with a mean elimination half-life of antimalarial activity of 43 min (95% CI, 33 to 53 min). Following oral administration to patients with acute falciparum malaria, peak antimalarial activity in plasma and the area under the plasma concentration-time curve were approximately double those during convalescence and the apparent volume of distribution and clearance were approximately half those during convalescence (P < or = 0.005). Acute malaria is associated with a significant reduction in the clearance of artesunate-associated antimalarial activity.
采用随机交叉设计，对19例急性非复杂性恶性疟原虫疟疾成年患者进行了口服和静脉注射青蒿琥酯（2mg/kg体重）的药代动力学特性研究。使用灵敏的生物测定法来测量血浆中由青蒿琥酯及其主要代谢产物双氢青蒿素产生的抗疟活性。在恢复期，对15例患者重复进行了口服研究。急性疟疾患者中抗疟药物的平均绝对口服生物利用度为61%（95%置信区间[CI]，52%至70%）。口服青蒿琥酯的吸收和消除迅速，抗疟活性的平均消除半衰期为43分钟（95%CI，33至53分钟）。对急性恶性疟患者口服给药后，血浆中的抗疟活性峰值和血浆浓度-时间曲线下面积约为恢复期的两倍，而表观分布容积和清除率约为恢复期的一半（P≤0.005）。急性疟疾与青蒿琥酯相关抗疟活性清除率的显著降低有关。
