Ohrt C, Watt G, Teja-Isavadharm P, Keeratithakul D, Loesuttiviboon L, Webster H K, Schuster B, Fleckenstein L
Department of Medicine, USA Medical Component, Armed Forces Research Institute of Medical Science (AFRIMS), Bangkok, Thailand.
Clin Pharmacol Ther. 1995 May;57(5):525-32. doi: 10.1016/0009-9236(95)90037-3.
The pharmacokinetics and tolerance of a 4.5 gm 7-day halofantrine loading dose regimen were evaluated in 10 Thai patients with malaria and in 10 noninfected volunteers. Halofantrine peak plasma concentrations and bioavailability on the first day of treatment were significantly lower in patients with malaria than in healthy volunteers. Halofantrine elimination half-life was significantly shorter in patients with malaria than healthy control subjects (9.5 versus 15.8 days). These data show a distinct effect of acute malaria on the absorption and elimination of the drug. In addition, marked intersubject and intrasubject variability in peak and trough halofantrine levels was observed, indicating variable drug absorption. This dosing regimen was effective and well tolerated, with mild transient diarrhea during the first few days of treatment in both groups. To produce consistently effective drug levels, the currently recommended dosing regimens may be suboptimal. Slow halofantrine elimination raises concern for induction of parasite resistance when the drug is used in endemic areas of the world.
对10名泰国疟疾患者和10名未感染志愿者评估了4.5克为期7天的卤泛群负荷剂量方案的药代动力学和耐受性。疟疾患者治疗第一天的卤泛群血浆峰值浓度和生物利用度显著低于健康志愿者。疟疾患者的卤泛群消除半衰期显著短于健康对照者（9.5天对15.8天）。这些数据显示急性疟疾对该药物的吸收和消除有明显影响。此外，观察到卤泛群峰值和谷值水平存在显著的个体间和个体内差异，表明药物吸收存在差异。该给药方案有效且耐受性良好，两组在治疗的头几天均出现轻度短暂腹泻。为了持续产生有效的药物水平，目前推荐的给药方案可能并非最佳。卤泛群消除缓慢引发了在世界流行地区使用该药物时诱导寄生虫耐药性的担忧。
