Orally formulated artemisinin in healthy fasting Vietnamese male subjects: a randomized, four-sequence, open-label, pharmacokinetic crossover study.
Orally formulated artemisinin in healthy fasting Vietnamese male subjects: a randomized, four-sequence, open-label, pharmacokinetic crossover study.
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DOI：
10.1016/j.clinthera.2011.04.017
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发表时间：
2011-05
影响因子：
3.2
通讯作者：
Ashton M
中科院分区：
文献类型：
--
作者：
Hien TT;Hanpithakpong W;Truong NT;Dung NT;Toi PV;Farrar J;Lindegardh N;Tarning J;Ashton M
青蒿素衍生物用于抗疟药物联合治疗。青蒿素和哌喹最近已被证明是治疗无并发症恶性疟原虫疟疾的联合疗法的潜在候选者。本研究的目的是评价相对生物利用度和表征的药物动力学特性的一种新的微粉化粉末制剂青蒿素对以前的标准越南配方时，作为一个单一的口服剂量或与哌喹组合。这是一项在空腹状态下在15名健康男性越南志愿者中进行的单中心、随机、4序列、开放标签、交叉研究，研究访视之间的洗脱期为3周。单次口服160或500 mg青蒿素，单独或与哌喹联合给药。潜在的不良事件由临床医生每天监测，并使用实验室检查结果。在给药后12小时内频繁采集血样。青蒿素定量血浆中使用LC-MS/MS。药代动力学参数计算从血浆浓度-时间曲线使用非房室分析方法。青蒿素新制剂的药代动力学参数Tmax、Cmax、AUC 0-∞、Vd/F、CL/F和t1/2（平均值[SD]）分别为1.83（0.88）h、178（97）ng/mL、504（210）h × ng/mL、1270（780）L、401（260）L/h和2.21（0.29）h。Cmax、AUC 0-last和AUC 0-∞经数学转换后的受试制剂/参比制剂比值的平均百分比分别为121%（90% CI，92.5-158）、122%（90% CI，101-148）和120%（90% CI，98.0-146）。这项单次给药研究发现，受试制剂和参比制剂之间的剂量标准化Cmax、AUC 0-last和AUC 0-∞平均几何差异相对较小（<40%），可能不会对疟疾感染的治疗产生临床影响。
Artemisinin derivatives are used in antimalarial drug combination therapy. Artemisinin and piperaquine have recently been proven to be prospective candidates for combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria. The goal of this study was to evaluate the relative bioavailability and to characterize the pharmacokinetic properties of a new micronized powder formulation of artemisinin against the previous standard Vietnamese formulation when administered as a single oral dose or in combination with piperaquine. This was a single-center, randomized, 4-sequence, open-label, crossover study conducted in 15 healthy male Vietnamese volunteers under fasting conditions with a washout period of 3 weeks between study visits. A single oral dose of 160 or 500 mg of artemisinin was administered alone or in combination with piperaquine. Potential adverse events were monitored daily by the clinician and by using laboratory test results. Frequent blood samples were drawn for 12 hours after dose. Artemisinin was quantified in plasma using LC-MS/MS. Pharmacokinetic parameters were computed from the plasma concentration–time profiles using a noncompartmental analysis method. Pharmacokinetic parameters Tmax, Cmax, AUC0-∞, Vd/F, CL/F, and t1/2 (mean [SD]) for the new formulation of artemisinin were 1.83 (0.88) hours, 178 (97) ng/mL, 504 (210) h × ng/mL, 1270 (780) L, 401 (260) L/h, and 2.21 (0.29) hours, respectively. The mean percentage of the test/reference formulation ratio for the logarithmically transformed values of Cmax, AUC0–last, and AUC0–∞ were 121% (90% CI, 92.5–158), 122% (90% CI, 101–148), and 120% (90% CI, 98.0–146), respectively. This single-dose study found that the dose-normalized Cmax, AUC0–last, and AUC0–∞ mean geometric differences between the test and reference formulations were relatively small (<40%) and will probably not have a clinical impact in the treatment of malaria infections.
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DOI：
10.4269/ajtmh.2007.76.641
发表时间：
2007-04-01
影响因子：
3.3
作者：
Alker, Alisa P.;Lim, Pharath;Meshnick, Steven R.
通讯作者：
Meshnick, Steven R.
DOI：
10.1016/0035-9203(92)90220-7
发表时间：
1992-07-01
影响因子：
2.2
作者：
ALIN, MH;BJORKMAN, A;ASHTON, M
通讯作者：
ASHTON, M
DOI：
10.1016/j.trstmh.2007.05.010
发表时间：
2007-10-01
影响因子：
2.2
作者：
Kongpatanakul, Supornchai;Chatsiricharoenkul, Somruedee;Sangvanich, Polkit
通讯作者：
Sangvanich, Polkit
影响因子：
3.4
作者：
Gordi, T;Xie, RJ;Ashton, M
通讯作者：
Ashton, M
DOI：
10.4269/ajtmh.1994.51.785
发表时间：
1994-12-01
影响因子：
3.3
作者：
DUC, DD;DEVRIES, PJ;VANBOXTEL, CJ
通讯作者：
VANBOXTEL, CJ