关键词: 三苯双脒, 青蒿琥酯, 蒿甲醚, 吡喹酮, 大鼠, 华支睾吸虫, 联合治疗

Abstract: Objective To assess the efficacy of single，multiple or combined oral doses of tribendimidine，artesunate，artemether and praziquantel against Clonorchis sinensis in rats. Methods A total of 147 rats，each infected with 50 C. sinensis metacercariae，were used in experimental chemotherapy. All the drugs used were administered intragastrically 42-44 d after infection. ① Sixty infected rats were randomly divided into 11 groups（4-5 rats per group）and the following drug dose-schedules were applied，i.e. under the same total dose tribendimidine or praziquantel was given at a single dose of 150 mg/kg，or given at smaller divided doses of 75 mg/kg（qd for 2 d），50 mg/kg（qd for 3 d），25 mg/kg（tid for 2 d）; artesunate or artemether was given at a single dose of 75 mg/kg，or given a half dose of 37.5 mg/kg daily for 2 days. ②Eighty-seven infected rats were randomly divided into 15 groups（4-6 rats per group） for combined treatment with the following drug administration regimens，i.e. artesunate or artemether 30 mg/kg plus praziquantel 150 mg/kg or tribendimidine 50 mg/kg and 75 mg/kg，respectively; tribendimidine 50 mg/kg plus praziquantel 150 mg/kg；tribendimidine 75 mg/kg plus praziquantel 187.5 mg/kg. A single dose of each drug mentioned above was also involved. Untreated C. sinensis-infected rats served as control. Rats were killed 14 days post-treatment，worms recovered from the bile duct and the liver tissue，mean worm burden reduction calculated and mean worm burden compared between the groups using non-parametric method（Mann-Whitney test）. Results Rats infected with C. sinensis and treated at a single 150 mg/kg dose of either tribendimidine or praziquantel resulted in a worm reduction of 57.2% and 63.8%，respectively. Whilst administration of tribendimidine at smaller but multiple doses given within 2-3 days at the same total dosage resulted in a slightly higher worm reduction（77.1%-79.4%），the opposite trend was observed for praziquantel（50.6%-54.2%）. However，for both tribendimidine and praziquantel，the difference of mean worm burden lacked statistical significance between single and multiple doses. Infected rats administered either artesunate or artemether at a single dose of 75 mg/kg or a daily dose of 37.5 mg/kg for 2 days，the worm reduction was 100% and 90.4%-98.5%，respectively. Combined treatment with low doses of tribendimidine(50 mg/kg or 75 mg/kg)plus praziquantel(150 mg/kg or 187.5 mg/kg)resulted in a worm reduction of 74.9%-100%, which were higher than those of 26.9%-79.6% obtained from a single dose of each drug used. High worm reduction of 74.4%-97.9% was also observed when administering a low dose of artesunate or artemether（30 mg/kg）plus a low dose of tribendimidine（50 mg/kg or 75 mg/kg）or praziquantel（150 mg/kg）. Mean worm reduction of 24.8%-79.6% were seen when drugs used at single doses. Conclusion The investigation confirmed that tribendimidine，artesunate，artemether and praziquantel are all efficacious against C. sinensis，and that drug combination acts synergistically.

Key words: Tribendimidine, Artesunate, Artemether, Praziquantel, Rat, Clonorchis sinensis, Combined treatment