Na-Bangchang K, Karbwang J, Palacios P A, Ubalee R, Saengtertsilapachai S, Wernsdorfer W H
Clinical Pharmacology Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
Eur J Clin Pharmacol. 2000 Jan;55(10):743-8. doi: 10.1007/s002280050008.
To assess the pharmacokinetics and relative bioavailability/bioequivalence of three commercial tablet formulations of mefloquine, i.e. Lariam (reference formulation), Mephaquin 100 Lactab and Eloquin-250, when given sequentially after dihydroartemisinin in Thai patients with acute uncomplicated falciparum malaria.
Twenty-nine Thai patients with acute uncomplicated falciparum malaria were randomised to receive an initial dose of 300 mg dihydroartemisinin, followed by 1250 mg mefloquine (at 24 h and 30 h after dihydroartemisinin) given as either Lariam (n=10 cases), Mephaquin (n=9 cases) or Eloquin-250 (n=10 cases). Serial blood samples were obtained up to day 42 after treatment with mefloquine. Mefloquine concentrations were determined in whole blood by means of ultraviolet high-performance liquid chromatography. The pharmacokinetic parameters of mefloquine were estimated using non-compartmental and compartmental analysis.
The three combination regimens were well tolerated. Patients in all treatment groups had a rapid initial response. However, nine patients (four and five cases in regimen containing Mephaquin 100 Lactab and Eloquin-250, respectively) had reappearance of parasitaemia during the follow-up period. Mefloquine from the three formulations showed significantly different pharmacokinetic and bioavailability metrics. Significantly lower peak plasma concentrations (C(max)) and areas under the plasma concentration-time curve (AUC; AUC(0-48h), AUC(0-7days), and total AUC) were observed with Mephaquin 100 Lactab than with the other two formulations. Mean values for relative bioavailability of the test to standard products were 49.1% (Mephaquin 100 Lactab) and 72.4% (Eloquine-250). Based on the criteria set, the bioavailability of the two test products (Mephaquin 100 Lactab and Eloquine-250) was considered non-equivalent to the reference product with respect to the rate (t(max), C(max)) and extent (AUC(0-48h), AUC(0-7days), total AUC) of mefloquine absorption.
评估在泰国急性非复杂性恶性疟患者中，青蒿琥酯之后依次给予甲氟喹的三种市售片剂制剂（即甲氟喹（参比制剂）、甲氟喹100乳酸片和依诺喹250）的药代动力学及相对生物利用度/生物等效性。
29例泰国急性非复杂性恶性疟患者被随机分组，先接受300mg青蒿琥酯的初始剂量，随后在青蒿琥酯给药后24小时和30小时给予1250mg甲氟喹，分别给予甲氟喹（参比制剂，10例）、甲氟喹100乳酸片（9例）或依诺喹250（10例）。在甲氟喹治疗后直至第42天采集系列血样。采用紫外高效液相色谱法测定全血中甲氟喹浓度。使用非房室和房室分析估算甲氟喹的药代动力学参数。
三种联合用药方案耐受性良好。所有治疗组患者均有快速的初始反应。然而，9例患者（含甲氟喹100乳酸片和依诺喹250的治疗方案中分别有4例和5例）在随访期内疟原虫血症复发。三种制剂的甲氟喹显示出显著不同的药代动力学和生物利用度指标。与其他两种制剂相比，甲氟喹100乳酸片的血浆峰浓度（C(max)）和血浆浓度-时间曲线下面积（AUC；AUC(0 - 48h)、AUC(0 - 7天)和总AUC）显著更低。受试产品相对于参比产品的相对生物利用度平均值分别为49.1%（甲氟喹100乳酸片）和72.4%（依诺喹250）。根据既定标准，两种受试产品（甲氟喹100乳酸片和依诺喹250）在甲氟喹吸收的速率（达峰时间(t(max))、C(max)）和程度（AUC(0 - 48h)、AUC(0 - 7天)、总AUC）方面被认为与参比产品不等效。
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