Evaluation of the safety and relative bioavailability of a new dihydroartemisinin tablet formulation in healthy Thai volunteers
Evaluation of the safety and relative bioavailability of a new dihydroartemisinin tablet formulation in healthy Thai volunteers
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DOI：
10.1016/j.trstmh.2007.05.010
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发表时间：
2007-10-01
影响因子：
2.2
通讯作者：
Sangvanich, Polkit
中科院分区：
文献类型：
--
作者：
Kongpatanakul, Supornchai;Chatsiricharoenkul, Somruedee;Sangvanich, Polkit
一种新的双氢青蒿素（DHA）片剂配方已开发出由泰国政府制药组织。本文以Dafra Pharma NV公司生产的DHA片剂为对照，对其体外溶出度、体内药代动力学以及健康志愿者的安全性进行了评价。采用两阶段交叉临床研究设计。24名志愿者被随机分配到两个序列（每个序列12名志愿者），接受200 mg单次口服剂量的GPO或Dafra制剂，洗脱期为5-7天。在体外，该制剂更容易溶解。在体内，该制剂的最大血浆浓度较高，生物利用度约高149%（90% CI 125-179%）。两种制剂均耐受良好。有趣的是，在施用一剂DHA（与基线相比血红蛋白降低0.73 g/dl和红细胞压积降低2.0%）或两剂DHA（与基线相比血红蛋白降低0.958/dl和红细胞压积降低3.3%）后，注意到血红蛋白和红细胞压积值显著降低（P< 0.001）。与单剂量相比，第二剂量与红细胞压积（P< 0.001）而不是血红蛋白的额外毒性相关。这一发现值得进一步研究，因为该药物将用于治疗疟疾，其后果是贫血。(C)2007年皇家热带医学和卫生学会。由爱思唯尔有限公司出版。保留所有权利。
Anew dihydroartemisinin (DHA) tablet formulation has been developed by the Thai Government Pharmaceutical Organization (GPO). In this report, its in vitro dissolution and in vivo pharmacokinetics as well as its safety in healthy volunteers were evaluated, using the DHA tablet made by Dafra Pharma NV as a reference. A two-period crossover clinical study design was utilised. Twenty-four volunteers were randomly allocated to two sequences (12 volunteers in each) to receive a 200mg single oral dose of either the GPO or Dafra formulation with a wash-out period of 5-7 days. In vitro, the GPO formulation dissolved more readily. In vivo, the GPO formulation had a higher maximum plasma concentration and approximately 149% (90% CI 125-179%) greater bioavailability. Both formulations were well tolerated. Interestingly, significant decreases in haemoglobin and haematocrit values (P< 0.001) were noted following administration of one dose of DHA (decrease of 0.73 g/dl haemoglobin and 2.0% haematocrit compared with baseline) or two doses of DHA (decrease of 0.958/dl haemoglobin and 3.3% haematocrit compared with baseline). The second dose was associated with additional toxicity compared with one dose with regard to haematocrit (P< 0.001) but not haemoglobin. This finding warrants further investigation, since the drug will be used for the treatment of malaria in which anaemia is a consequence. (C) 2007 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.