Diem Thuy L T, Ngoc Hung L, Danh P T, Na-Bangchang K
Faculty of Allied Health Sciences, Pharmacology and Toxicology Unit, Graduate Program in Biomedical Sciences, Thammasat University, Rangsit Campus, Pathumthani, Thailand.
Eur J Clin Pharmacol. 2008 Oct;64(10):993-8. doi: 10.1007/s00228-008-0506-6. Epub 2008 Jul 4.
The aim of the present study was to investigate the existence of time-dependent pharmacokinetics of artesunate (ARS) during 5 consecutive days of oral administration to 10 healthy Vietnamese subjects (aged 21-52 years and weighing 49-90 kg).
Each volunteer received 200 mg oral doses of ARS once daily for 5 consecutive days. Blood samples (3 ml each) were collected on days 1 and 5 at 0 (before dosing), 0.5, 1, 2, 3, 4, and 6 h after drug administration. During days 2, 3, and 4, the same volumes of blood were collected at 0, 1, 2, and 4 h after dosing. Plasma ARS and dihydroartemisinin (DHA) were measured using high-performance liquid chromatography-mass spectrometry (LC-MS).
Results did not show evidence of time-dependency for ARS or the active plasma metabolite DHA. There were no differences in the concentrations of ARS and DHA at all sampling times on days 1 and 5. In addition, the pharmacokinetics of both compounds were similar on days 1 and 5. This finding confirms that the enzyme auto-induction in drug metabolism may not be characteristic of the endoperoxide sesquiterpene antimalarial group.
本研究旨在调查10名健康越南受试者（年龄21 - 52岁，体重49 - 90 kg）连续5天口服青蒿琥酯（ARS）期间是否存在时间依赖性药代动力学。
每位志愿者连续5天每天口服200 mg的ARS。在第1天和第5天给药后0（给药前）、0.5、1、2、3、4和6小时采集血样（每次3 ml）。在第2、3和4天，给药后0、1、2和4小时采集相同体积的血液。使用高效液相色谱 - 质谱联用仪（LC - MS）测定血浆中的ARS和双氢青蒿素（DHA）。
结果未显示ARS或活性血浆代谢物DHA存在时间依赖性的证据。第1天和第5天所有采样时间点的ARS和DHA浓度均无差异。此外，两种化合物在第1天和第5天的药代动力学相似。这一发现证实药物代谢中的酶自诱导可能不是内过氧化物倍半萜抗疟药组的特征。
