Pharmacokinetics of artemisinin and artesunate after oral administration in healthy volunteers
Pharmacokinetics of artemisinin and artesunate after oral administration in healthy volunteers
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DOI：
10.4269/ajtmh.1997.56.17
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发表时间：
1997-01-01
影响因子：
3.3
通讯作者：
Plessas, ST
中科院分区：
文献类型：
--
作者：
Benakis, A;Paris, M;Plessas, ST
本研究旨在测定青蒿素（一种从黄花蒿中提取的天然物质）新剂型的药代动力学参数。植物）和其衍生物之一青蒿琥酯（12-羟基青蒿素的半琥珀酸酯）。这两种化合物被广泛用于治疗疟疾。这两种化合物的新口服形式（250 mg片剂）用于两项平行的药代动力学研究。青蒿素的平均药代动力学参数为：最大药物浓度（C-max）= 0.36 μ g/ml，达峰时间（t（max））= 100 min，表观半衰期（半衰期（t（1/2 max））= 0.62 h;分布半衰期（t（1/2 α））= 2.61 hr;下降半衰期（t（1/2 β））= 4.34 hr;浓度-时间曲线下总面积（AUC）= 1.19 mu g.hr/ml。青蒿琥酯的主要代谢物双氢青蒿素在血浆中可测得。双氢青蒿素的平均药代动力学参数为出现速率常数（K-a）= 2.11 hr（-1）;消除速率常数（K-e）= 1.18 hr（-1）;生物转化半衰期= 0.33 hr;消除半衰期= 0.65 hr; AUC = 0.74 mu g.hr/ml。两种药物形式均耐受良好，在任何受试者中均未观察到不良副作用。
This study was designed to determine the pharmacokinetic parameters of a new pharmaceutical form of artemisinin (a natural substance extracted from the Artemisia annua L. plant) and of one of its derivatives, artesunate, a semisuccinate of 12-hydroxy-artemisinin. These two compounds are widely used in the treatment of malaria. The new oral forms of these two compounds, in 250-mg tablets, were used in two parallel pharmacokinetic studies. For artemisinin, the mean pharmacokinetic parameters were maximum drug concentration (C-max) = 0.36 mu g/ml; peak time (t(max)) = 100 min; appearance half-life (t(1/2 max)) = 0.62 hr; distribution half-life (t(1/2 alpha)) = 2.61 hr; decline half-life (t(1/2 beta)) = 4.34 hr; and total area under the concentration-time curve (AUG) = 1.19 mu g.hr/ml. For artesunate, its main metabolite, dihydroartemisinin, was measurable in the plasma. The mean pharmacokinetic parameters for dihydroartemisinin were appearance rate constant (K-a) = 2.11 hr;(-1); elimination rate constant (K-e) = 1.18 hr(-1); biotransformation half-life = 0.33 hr; elimination half-life = 0.65 hr; and AUC = 0.74 mu g.hr/ml. Both pharmaceutical forms were well-tolerated and no undesirable side effects were observed in any of the subjects.