Pharmacy Faculty, Pará Federal University, Augusto Correa Street 01, Campus Universitário do Guamá, Belém, Pará, Brazil.
Laboratory of Public Health of Macapa, Av. Adilson José Pinto Pereira, 907, Macapá, Amapá, Brazil.
Malar J. 2018 Jul 16;17(1):268. doi: 10.1186/s12936-018-2416-0.
A fixed-dose combination of mefloquine with artesunate was evaluated in cases of falciparum malaria in the Brazilian Amazon basin with acceptable efficacy, safety and tolerability. However, there are no data on the pharmacokinetics of mefloquine in this coformulation in Brazil, which is valuable to evaluate whether Plasmodium is exposed to an effective concentration of the drug.
A prospective, single-arm study was conducted in male patients with slide-confirmed infection by Plasmodium falciparum using two tablets of a fixed-dose combination of artesunate (100 mg) and mefloquine base (200 mg) once daily and over 3 consecutive days. Serial blood samples were collected at admission and throughout 672 h post-administration of the drugs. Mefloquine was measured in each blood sample by high-performance liquid chromatography. The pharmacokinetic parameters were determined by non-compartmental analysis.
A total of 61 patients were enrolled in the study and 450 whole blood samples were collected for mefloquine measurement. The mefloquine half-life was 10.25 days, the maximum concentration (C) was 2.53 µg/ml, the area-under-the-curve (AUC) was 359 µgml h, the observed clearance (Cl/f) was 0.045 l/kg/h and the volume of distribution (V/f) was 14.6 l/kg. Mefloquine concentrations above 0.5 µg/ml were sustained for a mean time of 9.2 days.
The pharmacokinetic parameters of mefloquine determined in the study suggest an adequate exposure of parasite to mefloquine in the multiple oral dose regimen of the fixed dose combination of mefloquine and artesunate.
在巴西亚马逊流域，采用固定剂量复方制剂甲氟喹与青蒿琥酯治疗恶性疟，疗效、安全性和耐受性良好。然而，目前尚无该药在巴西的复方制剂药代动力学数据，而这对于评估疟原虫是否处于药物的有效浓度十分重要。
采用前瞻性、单臂研究方法，对经疟原虫镜检确认感染的男性患者进行研究，给予复方制剂青蒿琥酯（100mg）和甲氟喹碱（200mg）各 2 片，每日 1 次，连用 3 天。于给药前及给药后 672 小时内连续采集血样。采用高效液相色谱法检测全血中甲氟喹浓度。采用非房室分析方法计算药代动力学参数。
共有 61 例患者入组该研究，共采集 450 份全血样本用于检测甲氟喹浓度。甲氟喹半衰期为 10.25 天，最大浓度（C）为 2.53μg/ml，曲线下面积（AUC）为 359μgml·h，观察清除率（Cl/f）为 0.045 l/kg/h，表观分布容积（V/f）为 14.6 l/kg。甲氟喹浓度>0.5μg/ml 的持续时间平均为 9.2 天。
本研究中确定的甲氟喹药代动力学参数表明，采用甲氟喹与青蒿琥酯固定剂量复方制剂的多剂量口服方案，寄生虫可充分暴露于甲氟喹。
