Ittarat W, Looareesuwan S, Pootrakul P, Sumpunsirikul P, Vattanavibool P, Meshnick S R
Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand.
Antimicrob Agents Chemother. 1998 Sep;42(9):2332-5. doi: 10.1128/AAC.42.9.2332.
Thalassemia is common in Southeast Asia, where artemisinin derivatives are frequently used in the treatment of malaria. It has been previously reported that artemisinin derivatives can be concentrated by uninfected thalassemic erythrocytes in vitro but not by normal erythrocytes. As a follow-up to this report, we studied the antimalarial kinetics of intravascular artesunate (2.4 mg/kg of body weight) in 10 persons with normal hemoglobins and in 10 patients with thalassemia (2 with alpha-thalassemia type 1-hemoglobin Constant Spring and 8 with alpha-thalassemia type 1-alpha-thalassemia type 2). Concentrations of artesunate and its active metabolites in plasma were measured by bioassay and expressed relative to those of dihydroartemisinin, the major biologically active metabolite. Concentrations of intravascular artesunate in plasma peaked in both the normal individuals and the thalassemic individuals 15 min after injection (the first time point). Plasma drug concentrations at all time intervals, except that at 1 h, were significantly higher in thalassemic subjects than in normal subjects (P < 0.05). The area under the concentration-time curve was 9-fold higher (P < 0.001) and the volume of distribution at steady state was 15-fold lower (P < 0.001) in thalassemic than in normal subjects. In light of the potential neurotoxicity of artemisinin derivatives, these results suggest that thalassemic subjects may need a drug administration regimen different from that of normal patients.
地中海贫血在东南亚地区很常见，而青蒿素衍生物常用于该地区的疟疾治疗。此前已有报道称，未感染的地中海贫血红细胞在体外可浓缩青蒿素衍生物，而正常红细胞则不能。作为该报道的后续研究，我们对10名血红蛋白正常者和10名地中海贫血患者（2例α-地中海贫血1型-血红蛋白Constant Spring和8例α-地中海贫血1型-α-地中海贫血2型）进行了血管内青蒿琥酯（2.4mg/kg体重）抗疟动力学研究。通过生物测定法测量血浆中青蒿琥酯及其活性代谢物的浓度，并相对于主要生物活性代谢物双氢青蒿素的浓度进行表达。血管内青蒿琥酯在血浆中的浓度在正常个体和地中海贫血个体中均在注射后15分钟（第一个时间点）达到峰值。除1小时时外，地中海贫血受试者在所有时间间隔的血浆药物浓度均显著高于正常受试者（P<0.05）。地中海贫血受试者的浓度-时间曲线下面积比正常受试者高9倍（P<0.001），稳态分布容积比正常受试者低15倍（P<0.001）。鉴于青蒿素衍生物潜在的神经毒性，这些结果表明，地中海贫血受试者可能需要一种与正常患者不同的给药方案。
