Batty K T, Le A T, Ilett K F, Nguyen P T, Powell S M, Nguyen C H, Truong X M, Vuong V C, Huynh V T, Tran Q B, Nguyen V M, Davis T M
Department of Medicine, University of Western Australia, Fremantle Hospital.
Am J Trop Med Hyg. 1998 Nov;59(5):823-7. doi: 10.4269/ajtmh.1998.59.823.
To investigate the pharmacokinetic and pharmacodynamic properties of artesunate (ARTS) and its active metabolite dihydroartemisinin (DHA) in Plasmodium vivax infections, 12 male Vietnamese adults with slide-positive vivax malaria received either intravenous ARTS (120 mg; group 1) or oral ARTS (100 mg; group 2) with the alternative preparation given 8 hr later in a randomized, open, cross-over study. Following intravenous injection, ARTS had a peak plasma drug concentration (Cmax) of 35.6 microM (13.7 mg/L), an elimination half-life (t1/2) of 2.2 min, a clearance (CL) of 3.0 L/hr/kg, and a volume of distribution (V) of 0.16 L/kg. Dihydroartemisinin had a Cmax of 7.7 microM (2.2 mg/L), a tmax of 8 min, a t1/2 of 37 min, an apparent CL of 1.1 L/hr/kg, and an apparent V of 0.9 L/kg. Following oral ARTS, the mean relative bioavailability of DHA was 85%, the Cmax was 3.0 microM (0.85 mg/L), the tmax was 75 min, and t1/2 was 40 min. The mean time to 50% reduction in the parasite count (PCT50) and median fever clearance time were 3 hr and 16 hr, respectively. Following intravenous ARTS (group 1), the PCT50 for total parasites, rings, trophozoites, and gametocytes was 3.3 hr, 3.2 hr, 4.0 hr, and 3.6 hr, respectively. This study confirms that ARTS is effective against P. vivax, with rapid clearance of sexual and asexual forms of the parasite. Artesunate is a suitable initial treatment for vivax malaria, or when the plasmodial species cannot be reliably identified.
为研究青蒿琥酯（ARTS）及其活性代谢产物双氢青蒿素（DHA）在间日疟原虫感染中的药代动力学和药效学特性，在一项随机、开放、交叉研究中，12名间日疟原虫血片检查呈阳性的越南成年男性，分别接受静脉注射ARTS（120毫克；第1组）或口服ARTS（100毫克；第2组），8小时后给予另一种制剂。静脉注射后，ARTS的血浆药物峰浓度（Cmax）为35.6微摩尔/升（13.7毫克/升），消除半衰期（t1/2）为2.2分钟，清除率（CL）为3.0升/小时/千克，分布容积（V）为0.16升/千克。双氢青蒿素的Cmax为7.7微摩尔/升（2.2毫克/升），达峰时间（tmax）为8分钟，t1/2为37分钟，表观CL为1.1升/小时/千克，表观V为0.9升/千克。口服ARTS后，DHA的平均相对生物利用度为85%，Cmax为3.0微摩尔/升（0.85毫克/升），tmax为75分钟，t1/2为40分钟。寄生虫计数减少50%的平均时间（PCT50）和发热清除中位时间分别为3小时和16小时。静脉注射ARTS（第1组）后，总寄生虫、环状体、滋养体和配子体的PCT50分别为3.3小时、3.2小时、4.0小时和3.6小时。本研究证实，ARTS对间日疟原虫有效，可快速清除寄生虫的有性和无性形式。青蒿琥酯是间日疟的合适初始治疗药物，或在无法可靠鉴定疟原虫种类时使用。
