Antimalarial bioavailability and disposition of artesunate in acute falciparum malaria
Antimalarial bioavailability and disposition of artesunate in acute falciparum malaria
复制标题
DOI：
10.1128/aac.44.4.972-977.2000
复制
发表时间：
2000-04-01
影响因子：
4.9
通讯作者：
White, N
中科院分区：
文献类型：
--
作者：
Newton, P;Suputtamongkol, Y;White, N
采用随机交叉设计对19例急性无并发症恶性疟原虫疟疾成年患者口服和静脉注射青蒿琥酯（2 mg/kg体重）的药代动力学特性进行了研究。采用灵敏的生物测定法测定血浆中青蒿琥酯及其主要代谢物双氢青蒿素的抗疟活性。15例患者在恢复期重复口服研究。急性疟疾患者口服抗疟药的平均绝对生物利用度为61%（95%可信区间[CI]， 52 - 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 ~ 53分钟）。急性恶性疟疾患者口服该药后，血浆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，表观分布体积和清除率约为恢复期的一半（P <等于0.005）。急性疟疾与青蒿琥酯相关抗疟疾活性清除的显著减少有关。
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 less than or equal to 0.005). Acute malaria is associated with a significant reduction in the clearance of artesunate-associated antimalarial activity.