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. (2) Eighty-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.
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. (2) Eighty-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.