Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland.
J Antimicrob Chemother. 2011 Aug;66(8):1791-7. doi: 10.1093/jac/dkr178. Epub 2011 May 20.
Mefloquine has interesting antischistosomal properties, hence it might be an attractive partner drug for combination treatment with praziquantel. The aim of this study was to evaluate activities of mefloquine/praziquantel combinations against Schistosoma mansoni in vitro and in vivo.
Dose-response relationships were established following exposure of adult S. mansoni to mefloquine, praziquantel and fixed dose combinations of mefloquine/praziquantel in vitro. S. mansoni-infected mice were treated orally with selected doses of single drugs and drug combinations 7 weeks post-infection.
We calculated in vitro LC(50) values of 0.024 and 1.9 μg/mL for praziquantel and mefloquine, respectively. Mefloquine/praziquantel combinations showed synergistic effects, with combination index (CI) values <1 when adult S. mansoni were simultaneously incubated with both drugs in vitro. Reduced viabilities were also observed when schistosomes were first exposed to mefloquine followed by praziquantel in vitro. ED(50)s of 62 mg/kg and 172 mg/kg were determined for mefloquine and praziquantel against adult S. mansoni in vivo, respectively. Combinations of praziquantel (50 or 100 mg/kg) followed the next day by mefloquine (50 or 100 mg/kg) treatment revealed only moderate total worm burden reductions of 47.8%-54.7%. On the other hand, when both drugs (100 mg/kg each) were either given simultaneously or mefloquine was given prior to praziquantel, high total and female worm burden reductions of 86.0%-93.1% were observed. For the later treatment regimen, synergistic effects (CI < 1) were calculated when mefloquine and praziquantel were combined using a fixed dose ratio based on their ED(50)s.
Combinations of mefloquine and praziquantel may have clinical utility in the treatment of schistosomiasis.
甲氟喹具有有趣的抗血吸虫特性，因此它可能是与吡喹酮联合治疗的有吸引力的辅助药物。本研究的目的是评估甲氟喹/吡喹酮联合用药对曼氏血吸虫的体内外活性。
在体外暴露于甲氟喹、吡喹酮和甲氟喹/吡喹酮固定剂量组合的成年曼氏血吸虫后，建立剂量反应关系。感染曼氏血吸虫的小鼠在感染后 7 周口服给予选定剂量的单药和药物组合。
我们计算出吡喹酮和甲氟喹的体外 LC50 值分别为 0.024 和 1.9μg/mL。当同时在体外孵育两种药物时，甲氟喹/吡喹酮组合显示出协同作用，组合指数（CI）值<1。当体外先用甲氟喹处理后再用吡喹酮处理时，也观察到血吸虫的活力降低。体内，甲氟喹和吡喹酮分别对成年曼氏血吸虫的 ED50 值为 62mg/kg 和 172mg/kg。吡喹酮（50 或 100mg/kg）随后第二天用甲氟喹（50 或 100mg/kg）治疗的组合显示总虫荷减少仅为 47.8%-54.7%。另一方面，当两种药物（各 100mg/kg）同时给予或先用甲氟喹后用吡喹酮时，观察到总虫荷和雌虫荷的高减少率为 86.0%-93.1%。对于后一种治疗方案，当根据 ED50 以固定剂量比组合甲氟喹和吡喹酮时，计算出协同作用（CI<1）。
甲氟喹和吡喹酮的组合可能在治疗血吸虫病方面具有临床应用价值。
