tribendimidine and Clonorchiasis

Clonorchis sinensis is the most common human liver fluke in East Asia. Several studies proved its carcinogenesis in humans and it was reclassified as a group 1 biological carcinogen in 2009. It is still actively transmitted in endemic areas of Korea, China, Russia, and Vietnam. Currently it is estimated that more than 200 million people are at risk of infection, 15-20 million people are infected and 1.5-2 million show symptoms or complications. Several molecules and genes of the fluke have been identified and characterized. Studies on its oncogenesis and omics-based findings have been especially encouraging. Diagnosis of its infection depends mainly on detection of eggs in feces but other methods have been developed. ELISA using crude extract antigen is now popular for its diagnosis. Diagnosis by detecting DNAs from eggs in feces has been developed using PCR, real-time PCR, and LAMP, which have been found sensitive and specific. Imaging diagnosis has been studied in depth and is widely used. Any evidence of clonorchiasis, such as eggs, DNAs, or images, may lead to recommendations of chemotherapy in endemic areas. Praziquantel is the major chemotherapeutic agent for clonorchiasis and recently tribendimidine was found effective and is now under investigation as a promising chemotherapeutic alternative. Sustainable control programs which include mass chemotherapy with praziquantel and education for prevention of re-infection may reduce its morbidity and eliminate its infections in endemic areas.

Topics: Animals; Anthelmintics; Asia, Eastern; Asia, Southeastern; Clonorchiasis; Clonorchis sinensis; Enzyme-Linked Immunosorbent Assay; Feces; Host-Parasite Interactions; Humans; Nucleic Acid Amplification Techniques; Phenylenediamines; Polymerase Chain Reaction; Praziquantel; Real-Time Polymerase Chain Reaction; Russia

Currently praziquantel is one of the major drugs used in treatment of schistosomiasis and other trematode infections. Recent experimental studies indicate that a new anthelmintic, tribendimidine, is used in the treatment of intestinal nematodes, also possesses effect against several species of trematodes including Clonorchis sinensis, Opisthorchis viverrini and Echinostoma caproni. Tribendimidine is even more effective against C. sinensis in rats that a single 300 mg/kg oral dose cures almost all of the animals treated, a lower cure dose than praziquantel (375-500 mg/kg). The anti-malarial drugs artemether and artesunate are not only effective in the prevention of schistosomiasis, but also effective against several species of trematodes, especially C. sinensis. The single oral dose of both drugs to cure or achieve high efficacy in infected rats is 75 mg/kg. This review summarized research progress on tribendimidine, artesunate, and artemether in experimental animals infected with C. sinensis and other species of trematodes.

Topics: Animals; Anthelmintics; Artemether; Artemisinins; Artesunate; Clonorchiasis; Clonorchis sinensis; Cricetinae; Dogs; Phenylenediamines; Rats; Trematoda; Trematode Infections

Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.. We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment.. 156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel.. Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura.. Controlled-Trials.com ISRCTN55086560.

Topics: Adult; Animals; Anthelmintics; Ascariasis; Clonorchiasis; Coinfection; Female; Helminthiasis; Humans; Male; Mebendazole; Middle Aged; Phenylenediamines; Praziquantel

Clonorchiasis is of considerable public health importance, particularly in the People's Republic of China (PR China), where most of the 15 million individuals infected with Clonorchis sinensis are currently concentrated. Praziquantel is the drug of choice, but tribendimidine might be an alternative.. We performed a randomized open-label trial in Guangxi, PR China, to assess the efficacy and safety of 400 mg tribendimidine once, 400 mg tribendimidine daily for 3 days, and 75 mg/kg praziquantel in 1 day divided in 3 doses against parasitological-confirmed C. sinensis infections. Cure and egg reduction rates were determined 3 weeks posttreatment using available case analysis. Clinical symptoms were documented at baseline, and adverse events were recorded and graded 3 and 24 hours after each dose.. A total of 74 patients were included in the final analysis. Single-dose tribendimidine achieved a cure rate of 44%, whereas cure rates of 58% and 56% were obtained for tribendimidine administered for 3 days and praziquantel, respectively. High egg reduction rates (97.6%-98.8%) were observed for all treatment regimens. Single-dose tribendimidine was the best-tolerated treatment scheme. Patients treated with praziquantel experienced significantly more adverse events than did tribendimidine recipients (P < .05).. Tribendimidine has an efficacy comparable to praziquantel in the treatment of C. sinensis infection and resulted in fewer adverse events compared to praziquantel. Larger clinical trials are warranted among C. sinensis-infected patients to determine the potential of tribendimidine against clonorchiasis and other helminthiases. Clinical Trials Registration.Controlled-Trials.com, ISRCTN80829842.

Topics: Adult; Animals; Anthelmintics; China; Clonorchiasis; Clonorchis sinensis; Drug-Related Side Effects and Adverse Reactions; Feces; Female; Humans; Male; Middle Aged; Parasite Egg Count; Phenylenediamines; Praziquantel; Treatment Outcome

Tribendimidine (TBD) is a broad-spectrum anthelmintic drug that is also significantly effective in treating clonorchiasis. In this study, the altered metabolomes of Clonorchis sinensis (C. sinensis) in rats after TBD administration were quantified by using ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS) to explore the possible active sites of TBD against clonorchiasis through altered metabolites and metabolic pathway analysis, and the results are expected to provide a target for the future design of anti-Clonorchis sinensis drugs. The worm burden reduction rate and scanning electron microscopy demonstrated that praziquantel (PZQ, positive control drug) and TBD had significant effects on C. sinensis in rats after treatment at a single dose of 200 mg/kg for 24 h. For the MS-based metabolomic analysis, a total of 173 standard metabolites (126 amino acids, 10 phospholipids and 37 fatty acids) were utilized as a reference metabolite database for metabolome identification. In total, 32 amino acids, 71 phospholipids and 27 fatty acids were detected in the C. sinensis of each group. Among these metabolites, 10 amino acids were significantly decreased in both drug-treated groups. Four lysophosphatidyl cholines (LPCs), six lysophosphatidyl ethanolamines (LPEs) and one phosphatidyl inositol (PI) were significantly increased after treatment with TBD. There were no significant changes in fatty acids among the control group and the two drug-treated groups. The results indicated that TBD administration caused a decrease in amino acids involved in the metabolic pathways of energy consumption and an increase in lysophospholipids, which are the hydrolysis products of phospholipase2 (PLA2) in the phospholipid metabolic pathways. The increased lysophospholipid content can destroy the cell membrane, increase membrane permeability, and even cause exposure to internal antigens that can be attacked by host antibodies. Perhaps the destroyed membrane, the exposed internal antigens and the consumed energy are the cause of the damage and death of C. sinensis after TBD administration. This is an interesting problem that can be examined in future research.

Topics: Amino Acids; Animals; Clonorchiasis; Clonorchis sinensis; Fatty Acids; Metabolome; Phenylenediamines; Phospholipids; Rats; Tandem Mass Spectrometry

The aim of the study is to understand the anti-Clonorchis sinensis properties of mebendazole and albendazole, and compare to praziquantel and tribendimidine. Two hundred and thirty rats were divided into five batches for experimental treatment. In four batches, each rat was infected orally with 50 or 100 C. sinensis metacercariae. Twenty-eight to 46 days post-infection, groups of rats were treated orally with single doses of mebendazole, albendazole, praziquantel, tribendimidine, or multiple daily doses of albendazole. While in the remaining batch, mebendazole or praziquantel was administered to groups of rats infected each with 50 metacercariae for 7 or 14 days. In each batch of test, untreated but infected rats served as control. All rats were euthanized 2-4 weeks post-drug administration for assessment of efficacy. In the first batch of test, rats treated with mebendazole or tribendimidine at single doses of 150, 75, and 37.5 mg/kg resulted in worm burden reductions of 99.0%, 94.0%, and 73.1%, or 98.0%, 80.6%, and 60.4%, respectively. When rats were treated with albendazole at the same dose levels, no or poor effect was seen. In the second batch of test, promising effect against adult C. sinensis in rats treated with mebendazole or tribendimidine at single doses of 100 and 50 mg/kg were also observed, but under the single dose of 25 mg/kg, only tribendimidine still remained the effect. In the third batch of test, the aforementioned three single dose levels of mebendazole, albendazole and praziquantel were applied. Again, mebendazole exhibited higher effect and albendazole exhibited no or poor effect. While praziquantel, administered at a higher dose of 300 mg/kg, also showed promising effect. In the fourth batch of test, oral administration of albendazole at a daily dose of 150 or 100 mg/kg for 2 or 3 days resulted in moderate or higher efficacy with worm burden reductions of 79.2% and 91.9%, respectively. In the fifth batch of test, single mebendazole doses of 150 or 75 mg/kg exhibited promising effect against 14-day-old C. sinensis in rats with worm burden reductions of 95.3% and 86.4%, respectively, but mebendazole was short of the effect against 7-day-old worms. Under the same dose level, praziquantel possessed an effect against both 7- and 14-day-old juvenile C. sinensis. The results confirm that in infected rats, mebendazole administered orally at a single dose of 150 mg/kg exhibits potential effect against juvenile (14-day-old) and adult C. sine

Topics: Albendazole; Animals; Antiprotozoal Agents; Clonorchiasis; Clonorchis sinensis; Disease Models, Animal; Male; Mebendazole; Metacercariae; Phenylenediamines; Praziquantel; Rats; Rats, Sprague-Dawley

We investigated the morphological effects of half-strength treatments with praziquantel, artemether, artesunate, OZ78 and tribendimidine as well as combinations of praziquantel with artemether, artesunate, OZ78 and tribendimidine and an artesunate-tribendimidine combination in rats harboring adult Clonorchis sinensis. Rats were infected with C. sinensis, dosed orally with single agents or combination treatments and flukes recovered at 3 or 5 days post-treatment. The number of flukes was counted, the viability recorded and surface changes monitored by scanning electron microscopy. Drug effects induced by the individual drugs at sub-curative doses 3 days post-treatment were minor with the exception of flukes recovered from rats treated with artemether and tribendimidine. Treatment with the praziquantel combinations of artesunate, OZ78 and tribendimidine did not produce a greater disruption of the tegument than the individual drugs 3 days post-treatment. On the other hand, at this time point many worms treated with artemether-praziquantel had died and eruptions, roughening or blebbing were observed on all worms examined. Five days post-treatment flukes exposed to any of the praziquantel combinations in rats had died. Rats treated with an artesunate-tribendimidine combination resulted in a rapid death of flukes, 3 days post-treatment all worms had been expelled. In conclusion, we have confirmed the promising clonorchicidal properties of different drug combinations in rats. Differences in the extent and time-scale of tegumental disruption have been observed. The effect of drug combinations against C. sinensis requires further scientific inquiry, e.g. in transmission electron microscopy studies and in the C. sinensis-rabbit model.

Topics: Adamantane; Animals; Anthelmintics; Artemether; Artemisinins; Artesunate; Clonorchiasis; Clonorchis sinensis; Drug Therapy, Combination; Female; Microscopy, Electron, Scanning; Phenylenediamines; Praziquantel; Rats; Rats, Wistar; Skin; Treatment Outcome

To evaluate the efficacy in treatment of Clonorchis sinensis-infected rats using the administration regimens of tribendimidine, artesunate and praziquantel applied in clinical treatment of clonorchiasis.. The doses of tribendimidine, artesunate and praziquantel used in clinical treatment of clonorchiasis were converted to the doses used in rats by the method of equal effective dose conversion among different animals, while the administration regimens of the drugs were designed basing on the regimens used in clinical trials. Thus, the following dose schedules were set up, i.e., tribendimidine 16 or 32 mg/(kg x d) x 1, 2 or 3 d (bid), 8 or 16 mg/(kg x d) x 3 d; artesunate 12 mg/(kg x d) x 3 d (tid) and 16 mg/(kg x d) x 3 d (bid); praziquantel 143 mg/(kg x d) x 2 or 3 d (tid), 143 mg/(kg x d) x 2 or 3 d (bid), 47.7 or 71.5 mg/(kg x d) x 3 d. 151 rats were divided into 2 batches and each rat was infected orally with 50 metacercariae of C. sinensis. In the first batch of test, 79 rats were divided into 13 groups of 5-6 rats 5 weeks post-infection. Among them 6 groups were treated orally only with tribendimidine, artesunate or praziquantel, while other 7 groups were treated with tribendimidine combined with artesunate or praziquantel, or praziquantel combined with artesunate. The remaining 8 untreated rats served as control. In the second batch of test, 72 rats were divided into 13 groups of 5 rats. Among them, 7 and 6 groups were treated with tribendimidine and praziquantel, respectively, 6 weeks post-infection. The remaining 8 untreated rats served as control. Rats were sacrificed 14 days post-treatment, worms were recovered from the bile duct and the liver tissue. The mean worm reduction rate was calculated and compared among the groups by non-parametric method (Mann-Whitney test).. In the first batch of test, the mean worm burdens in rats infected with C. sinensis and treated orally with tribendimidine 16 or 32 mg/(kg x d) x 3 d (bid), praziquantel 143 mg/(kg x d) x 3 d (tid), or 143 mg/(kg x d) x 3 d (bid) were significantly lower than that of the control (P < 0.01) with mean worm burden reductions of 94.2%-96.0%. No efficacy was seen when infected rats were treated orally with artesunate 12 mg/(kg x d) x 3 d (tid). But in those treated with artesunate 16 mg/(kg x d) x 3 d (bid), the mean worm burden was significantly lower than that of the control (P < 0.05) with a mean worm reduction of 57.2%. In combined treatment, the infected rats treated with tribendimidine 16 or 32 mg/(kg x d) x 3 d (bid) in combination with praziquantel 143 mg/(kg x d) x 3 d(bid) or artesunate 16 mg/(kg x d) x 3 d (bid), the difference of mean worm burden between each combined treatment group and control group was statistically significant (P < 0.01) with mean worm reductions of 94.2% -99.4% which revealed that the worm reduction rate in combined treatment group was similar to the corresponding group treated with tribendimidine or praziquantel alone, but significantly higher than that of the group treated with artesunate alone. In infected rats treated with praziquantel 143 mg/(kg x d) x 3 d (tid) plus artesunate 12 mg/(kg x d) x 3 d (tid) or praziquantel 143 mg/(kg x d) x 3 d (bid) plus artesunate 16 mg/(kg x d) x 3 d (bid), the mean worm burden reductions were 93.6% -100%. In the second batch of test, the efficacy of tribendimidine obtained from infected rats treated with the drug 16 or 32 mg/(kg x d) x 2 d (bid) and 3 d (bid), the difference of mean worm burdens between them was not statistically significant with mean worm reductions of 86.5%-95.1%. When rats were treated with tribendimidine 32 mg/(kg x d) x 1 d (bid), the mean worm reduction was 73.0%, while the dose of the drug was given to the rats at 8 or 16 mg/kg daily for 3 days the mean worm reduction rates were 88.3%-92.6%. Treatment of praziquantel 143 mg/(kg x d) x 3 d (tid) resulted in a worm reduction of 96.9%, if the treatment course reduced to 2 d, the rate was 63.2%. Similar results were obtained in rats treated with praziquantel 143 mg/(kg x d) x 2 d (bid) and 3 d (bid). Finally, administration of praziquantel at a daily dose of 47.7 or 71.5 mg/kg for 3 d exhibited no effect against C. sinensis.. When the dose schedules of tribendimidine, artesunate and praziquantel used in humans are converted to the doses for use in rats, tribendimidine and praziquantel exhibit satisfactory effect against C. sinensis, but artesunate shows no or less effect; the treatment course of tribendimidine can be reduced from 3 d to 2 d. Since tribendimidine and praziquantel used alone have endorsed high efficacy against C. sinensis in rats, combinations among the 3 drugs do not show better effect.

Topics: Animals; Anthelmintics; Artemisinins; Artesunate; Clonorchiasis; Clonorchis sinensis; Male; Phenylenediamines; Praziquantel; Rats; Rats, Sprague-Dawley

The tegument of trematodes plays a key role in nutrient absorption, exerts secretory functions, protects the parasite against the immune system of the host, and is a target for anti-trematocidal drugs. We performed a temporal examination of tegumental changes following artemether and tribendimidine administration on adult Clonorchis sinensis in rats using scanning electron microscopy. Rats infected with C. sinensis for 6 weeks were treated orally with a single dose of artemether (150 mg/kg) or tribendimidine (300 mg/kg). Worms were collected between 8 h and 7 days (artemether) and between 4 h and 2 days post-treatment (tribendimidine). Worms recovered from untreated rats served as controls. Eight hours after artemether administration, the tegument of C. sinensis was extensively disrupted, including severe swelling, fusion and vacuolization, and the suckers were damaged. Four hours after administration of tribendimidine, C. sinensis worms showed extensive tegumental alterations, characterized by massive sloughing, and the suckers were damaged. Interestingly, the severity of tegumental changes did not progress further with time. Our results show that both artemether and tribendimidine rapidly disrupt the tegument and damage the suckers of adult C. sinensis. The subtle differences in tegumental changes induced by artemether and tribendimidine might indicate different mechanisms of action of these drugs against C. sinensis.

Topics: Animal Structures; Animals; Anthelmintics; Artemether; Artemisinins; Clonorchiasis; Clonorchis sinensis; Male; Microscopy, Electron, Scanning; Phenylenediamines; Rats; Time Factors

Caused by the Chinese liver fluke Clonorchis sinensis, clonorchiasis is of growing public health importance. Treatment and control of the disease rely on a single drug, praziquantel, and little information regarding combination chemotherapy is available. Here, we evaluated the in vivo efficacy of praziquantel combined with artemether, artesunate, OZ78, and tribendimidine, as well as an artesunate-tribendimidine combination against C. sinensis, in a rat model. Data from previous experiments were included, and negative binomial regression analyses were carried out to determine dose-response relationships and to study the effect of drug combination. All drugs given in monotherapy were efficacious in killing the worms; doses of 16 and 70 mg/kg of body weight of artesunate, for example, reduced worm burden by 50% and 95%, respectively. Artemether and OZ78 (12.5 to 50 mg/kg) showed dose-dependent killing of worms but no significant drug interactions when given with 150 mg/kg praziquantel, suggesting independent additive effects. In contrast, artesunate and tribendimidine (12.5 to 50 mg/kg) showed synergistic interactions with 150 mg/kg praziquantel. When low doses of 3.1 and 6.25 mg/kg OZ78 and artemether, respectively, were combined with praziquantel (150 mg/kg) an increased worm survival, above the level observed with praziquantel monotherapy, was noted. A similar antagonism was seen when praziquantel (75 mg/kg) was combined with several of the companion drugs at various doses. In conclusion, in vivo efficacy of praziquantel, the artemisinins, OZ78, and tribendimidine against C. sinensis is confirmed, and combination chemotherapy with praziquantel produces synergistic and antagonistic effects depending on the doses administered. Further preclinical investigations are warranted.

Topics: Adamantane; Animals; Anthelmintics; Artemether; Artemisinins; Artesunate; Clonorchiasis; Clonorchis sinensis; Female; Phenylenediamines; Praziquantel; Rats; Rats, Wistar

The purpose of the study was to understand the in vitro and in vivo effect of tribendimidine (TBD) and its metabolites of p-(1-dimethylamino ethylimino)aniline (aminoamidine, deacylated amidantel, BAY d 9216, dADT), acetylated dADT (AdADT), terephthalaldehyde (TPAL), and terephthalic acid (TPAC) against adult Clonorchis sinensis. In in vitro test, the adults of C. sinensis were placed to each of the 24 wells of a Falcon plate and maintained in Hanks' balanced salt solution-20% calf serum. Besides observation on the direct in vitro effect of TBD and its metabolites, the worms exposed to TBD and its metabolites for 1-24 h were transferred to the medium without drug and incubated continually for another 72 h. The reversible effect of TBD and its metabolites was assessed by the recovery of worm motor activity and parasite survival. In in vivo test, 235 rats were divided into five batches for oral infection of each rat with 50 C. sinensis metacercariae. Five to 6 weeks post-infection, groups of rats were treated orally or intramuscularly with a single dose of TBD or its metabolites, while untreated but infected rats served as control. All treated rats were killed 2 weeks post-treatment for assessment of efficacy. When adult C. sinensis were exposed to TBD or dADT 0.5 microg/mL, they were paralyzed rapidly accompanied by dilatation of the gut. The in vitro effect of AdADT decreased significantly, which was at least lower than 20- to 40-fold compared with TBD and dADT. TPAL and TPAC at a high concentration of 100 microg/mL exhibited no effect against adult C. sinensis. In the worms exposed to TBD or dADT 1 microg/mL for 1 h, well recovery of the worm motor activity from paralysis was seen in the medium without drug. If exposure time extended to 4-24 h before transferred to the medium without drug, few worms were dead and most worms showed very poor recovery of their activity. When the worms exposed to TBD or dADT 10 microg/mL for 1, 4, and 24 h were transferred to the drug-free medium, recovery of poor motor activity of worms or worm death was seen. In the worms exposed to AdADT 20 and 40 microg/mL for 1-24 h, more worms recovered poor motor activity in the medium without drug. In rats infected with C. sinensis and treated orally with TBD or dADT, the ED(50) and ED(95) were 20.318 and 195.358 mg/kg or 18.969 and 268.882 mg/kg. Under the equal dosages used in the treatment of rats infected with C sinensis, the effects between TBD and dADT or TBD and AdADT were si

Topics: Administration, Oral; Animals; Anthelmintics; Clonorchiasis; Clonorchis sinensis; Injections, Intramuscular; Locomotion; Male; Molecular Structure; Phenylenediamines; Rats; Rats, Sprague-Dawley; Survival Analysis; Treatment Outcome

To observe the effect of tribendimidine, artesunate and praziquantel in treatment of hamsters (Mesocricetus auratus) infected with Clonorchis sinensis.. A total of 93 hamsters, each infected with 30 C. sinensis metacercariae, were treated intragastrically with above-mentioned drugs at a single dose. (1) In order to observe the effect of the drugs against juvenile C. sinensis, 20 out of 31 infected hamsters were randomly divided into 4 groups (5 hamsters per group) 14 d post-infection: artesunate 300 mg/kg, tribendimidine 100 mg/kg or 200 mg/kg, and praziquantel 200 mg/kg. Other 6 hamsters were divided equally into 2 groups 24 d post-infection and treated with tribendimidine 200 mg/kg and artesunate 300 mg/kg, respectively. The remained 5 untreated hamsters served as control. (2) Twenty-two hamsters were randomly divided into 5 groups (4-5 hamsters per group) 28 d post-infection and treated with tribendimidine 25 mg/kg or 50 mg/kg, artesunate 25 mg/kg and praziquantel 50 mg/kg, respectively. Other untreated hamsters served as control. (3) Forty hamsters 28 d after infection were randomly divided into 8 groups (4-6 hamsters per group) and treated with tribendimidine 50 mg/kg, 100 mg/kg or 200 mg/kg, artesunate 100 mg/kg or 200 mg/kg, praziquantel 100mg/kg or 200mg/kg, respectively. The remained hamsters served as control. All hamsters were sacrificed 14 d post-treatment and worms were recovered from the bile duct and liver tissue. The mean worm burden and its reduction were calculated. The differences of mean worm burden between each treated group and the corresponding control were analyzed statistically.. In hamsters infected with 14-d-old C. sinensis and treated orally with tribendimidine at a single dose of 100 or 200 mg/kg, the mean worm burdens were significantly lower than that of the control (P<0.01) with a worm reduction of 90.6% and 85.9% respectively. The mean worm burden obtained from the infected hamsters treated with praziquantel at a single dose of 200 mg/kg was also significantly lower than that of the control (P<0.05) with a worm reduction of 71.9%. However, the difference of mean worm burden between artesunate and control groups was not statistically significant. The juvenile parasites developed into adult worms 24 d after infection. By administering tribendimidine 200 mg/kg to the adult C. sinensis-infected hamsters, the mean worm burden was significantly lower than that of the control (P<0.01) with a worm reduction of 89.8%. Whilst the administration of artesunate at a higher dose of 300 mg/kg, all hamsters were cured. Further tests indicated that tribendimidine in a lower dose of 25 mg/kg to the hamsters 28 d after infection resulted in a significantly lower mean worm burden compared to the control (P<0.05) with a worm reduction of 71.8%. With an increased dose of tribendimidine 100 mg/kg, all hamsters were cured. The worm reduction was only 20.0% and 56.4% when 25 mg/kg and 100 mg/kg of artesunate were administered. With 200 mg/kg artesunate, the worm reduction reached as high as 98.5% and the mean worm burden was significantly lower than that of the control (P<0.01). Furthermore, administration of praziquantel at a dose of 100 mg/kg or 200 mg/kg at 28 d post-infection resulted in a significantly lower mean worm burden than that of the control (P<0.05) with a worm reduction of 78.9% and 83.5% respectively.. In hamster model, tribendimidine and praziquantel exhibit promising effect against both juvenile and adult C. sinensis, while artesunate is only efficacious against adult worms.

Topics: Animals; Anthelmintics; Artemisinins; Artesunate; Clonorchiasis; Clonorchis sinensis; Cricetinae; Mesocricetus; Phenylenediamines; Praziquantel; Treatment Outcome

To assess the efficacy of single, multiple or combined oral doses of tribendimidine, artesunate, artemether and praziquantel against Clonorchis sinensis in rats.. 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).. 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.. The investigation confirmed that tribendimidine, artesunate, artemether-and praziquantel are all efficacious against C. sinensis, and that drug combination acts synergistically.

Topics: Animals; Anthelmintics; Artemether; Artemisinins; Artesunate; Clonorchiasis; Clonorchis sinensis; Drug Therapy, Combination; Female; Male; Parasitic Sensitivity Tests; Phenylenediamines; Praziquantel; Random Allocation; Rats; Rats, Sprague-Dawley

We examined the in vivo activity of tribendimidine against selected trematodes. A single 150-mg/kg dose of tribendimidine achieved a 99.1% reduction of Clonorchis sinensis in rats. A 400-mg/kg dose of tribendimidine reduced Opisthorchis viverrini in hamsters by 95.7%. High doses of tribendimidine showed no activity against Schistosoma mansoni and Fasciola hepatica.

Topics: Animals; Anthelmintics; Clonorchiasis; Clonorchis sinensis; Cricetinae; Fasciola hepatica; Fascioliasis; Female; Male; Mesocricetus; Mice; Opisthorchis; Phenylenediamines; Rats; Rats, Wistar; Schistosoma mansoni; Schistosomiasis mansoni