THE PHARMACOKINETICS OF A SINGLE-DOSE OF ARTEMISININ IN HEALTHY VIETNAMESE SUBJECTS
THE PHARMACOKINETICS OF A SINGLE-DOSE OF ARTEMISININ IN HEALTHY VIETNAMESE SUBJECTS
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DOI：
10.4269/ajtmh.1994.51.785
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发表时间：
1994-12-01
影响因子：
3.3
通讯作者：
VANBOXTEL, CJ
中科院分区：
文献类型：
--
作者：
DUC, DD;DEVRIES, PJ;VANBOXTEL, CJ
在 12 名健康越南男性受试者单次口服 500 毫克青蒿素后，研究了青蒿素的药代动力学。在服药后 48 小时内，每个受试者总共获得了 14 个血浆样本。采用高效液相色谱法和电化学检测法测定青蒿素浓度。通过记录主观和客观结果来评估耐受性，包括重复体检、血常规检查和心电图。浓度-时间曲线的拟合和药代动力学计算揭示了以下结果：平均+/-SD分布体积/剂量比为19.4+/-6.9L/kg，平均+/-SD吸收半衰期为0.58+/-0.54小时，平均+/-SD计算的最大浓度为391+/-147μg/L，发生在药物摄入后1.81+/-0.73小时。消除很快，平均+/-SD消除半衰期为2.59+/-0.55小时。尽管生物利用度似乎非常低，但峰浓度足以发挥抗疟活性。药代动力学相对较小的个体差异似乎不具有临床意义。对单剂量青蒿素的耐受性良好：未检测到不良反应。根据这些结果，可以建议每天 2 x 500 mg 青蒿素（口服剂量）的治疗方案。尽管生物利用度差，但这将导致足够的抗疟血浆浓度和快速消除。
The pharmacokinetics of artemisinin was studied in 12 healthy male Vietnamese subjects after a single, 500-mg, oral dose. A total of 14 plasma samples per subject was obtained up to 48 hr after drug intake. Measurement of artemisinin concentration was performed by high-performance liquid chromatography with electrochemical detection. Tolerance was evaluated by recording subjective and objective findings including repeated physical examination, routine blood investigation, and electrocardiograms. Fitting of the concentration-time curve and pharmacokinetic calculations revealed the following results: a mean +/- SD volume of distribution/dose ratio of 19.4 +/- 6.9 L/kg, a mean +/- SD absorption half-life of 0.58 +/- 0.54 hr with a mean +/- SD calculated maximum concentration of 391 +/- 147 mu g/L occurring at 1.81 +/- 0.73 hr after drug intake. Elimination was rapid, with a mean +/- SD elimination half-life of 2.59 +/- 0.55 hr. Peak concentrations were sufficient with regard to antimalarial activity although bioavailability appears to be very low. The relatively small interindividual variation in pharmacokinetics does not seem to be of clinical significance. Tolerance to the single dose of artemisinin was good: no adverse effects were detected. Based on these results, a treatment schedule of 2 x 500 mg of artemisinin (oral dose) per day can be advised. This will result in adequate antimalarial plasma concentrations, despite poor bioavailability, and rapid elimination.