Anthelmintic Activity of Triclabendazole

Gc, Coles

doi:10.1017/s0022149x00026110

Cited by 49 publications

(22 citation statements)

References 11 publications

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“…For comparison, a slightly lower dose (40 mg/kg) of triclabendazole, the drug of choice for fascioliasis, reduced adult worm burdens by 99% in F. hepatica-infected rats. 13 Similar to triclabendazole, but in contrast to several existing fasciolicides such as closantel or closurlon 14 OZ78 showed excellent activity against juvenile F. hepatica; a single oral dose of 100 mg/kg cured juvenile F. hepatica infections harboured in rats.…”

Section: Discussionmentioning

confidence: 99%

The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica

Keiser

Utzinger

Tanner

et al. 2006

Journal of Antimicrobial Chemotherapy

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Objectives:The trematocidal properties of a synthetic peroxide, 1,2,4-trioxolane (OZ78) were determined both in vivo and in vitro.Methods: Two weeks post-infection Echinostoma caproni-infected mice were administered single oral doses of 400-1000 mg/kg OZ78. Fasciola hepatica-infected rats were treated orally with 50-400 mg/kg OZ78 3 and 8-9 weeks post-infection. Worm burden reductions were assessed against untreated control animals. Adult F. hepatica were observed by scanning electron microscopy (SEM) after recovery from the bile duct of a rat 3 days after administration of a single oral dose of 100 mg/kg OZ78 and after in vitro exposure to concentrations of 1, 10 and 100 mg/mL OZ78. Results:In the E. caproni-mouse model 100% worm burden reductions were achieved with a single oral dose of 1000 mg/kg OZ78. A single dose of 100 mg/kg OZ78 resulted in worm burden reductions of 100% against juvenile and adult F. hepatica. F. hepatica recovered from rats 3 days post-treatment displayed feeble activity and some flukes had died. Typical features revealed by SEM included extensive blebbing and sloughing. Exposure of F. hepatica to 10-100 mg/mL OZ78 in vitro resulted in the death of all trematodes. F. hepatica showed focal blebbing and sloughing of the tegument at all concentrations investigated.Conclusions: Our data indicate that OZ78 is highly efficacious against F. hepatica and E. caproni and provide a sound platform for identification of a synthetic peroxide drug development candidate against major trematode infections.

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Section: Discussionmentioning

confidence: 99%

The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica

Keiser

Utzinger

Tanner

et al. 2006

Journal of Antimicrobial Chemotherapy

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“…Whole flukes were transferred to fresh NCTC culture medium containing triclabendazole sulphoxide at a concentration of 15 lg/ ml or 50 lg/ml. The former concentration corresponds to maximum blood levels in vivo (13.3 lg/ml following a dose of 10 mg/kg in sheep: Hennessy et al 1987); the latter to the highest concentration used in vitro (Coles 1986). The drug was initially prepared as a stock solution in dimethyl sulphoxide and added to the culture medium to give a final solvent concentration of 0.1% (v/v).…”

Section: In Vitro Drug Treatmentmentioning

confidence: 99%

Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro

Walker¹,

McKinstry²,

Boray

et al. 2004

Parasitol Res

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In this study, the susceptibility of two isolates of Fasciola hepatica--the Fairhurst and Oberon isolates--to treatment with triclabendazole was investigated, both in vivo and in vitro. The Fairhurst isolate originated in England, but has since been maintained in Australia; the Oberon isolate originated in Australia. Triclabendazole had a very high efficacy against the Fairhurst isolate. In sheep (dose: 10 mg/kg), the efficacy ranged from 78.4% at 2 weeks post-infection to 98.5% at 6 weeks post-infection. In cattle (dose: 12 mg/kg) efficacy was 89% at 2 weeks post-infection and 100% at 12 weeks. In contrast, against the Oberon isolate, triclabendazole had 0% efficacy against 2-week-old flukes in sheep (dose: 10 mg/kg) and 5% against 4-week-old flukes. Surface changes to flukes of the two isolates were assessed by scanning electron microscopy following treatment in vitro for 24 h in triclabendazole sulphoxide (15 and 50 microg/ml). Disruption took the form of blebbing, swelling and furrowing of the tegument and was greater in the Fairhurst than the Oberon isolate. Surface changes generally were more severe in the anterior than posterior region of the fluke and the dorsal surface was also consistently more severely affected than the ventral surface. Disruption was more severe at the higher drug concentration for both isolates. The morphological data is consistent with the efficacy data, which indicates that the Fairhurst isolate of F. hepatica is susceptible to triclabendazole treatment, whilst the Oberon isolate is refractory.

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“…Interestingly, TCBZ does not bind to colchicine in F. hepatica homogenates [10]. It is likely that a different site of action is involved on the flukicidal activity of TCBZ, which could also explain its lack of efficacy against other helminth parasites [11,12]. The exact mode of action of TCBZ and the flukicidal potency of the parent drug and its metabolites await elucidation.…”

Section: Introductionmentioning

confidence: 97%

Measurement of triclabendazole and its metabolites in liver flukes: method development and full validation

Mottier¹,

Moreno²,

Álvarez³

et al. 2004

Journal of Pharmaceutical and Biomedical Analysis

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Anthelmintic Activity of Triclabendazole

Cited by 49 publications

References 11 publications

The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica

The synthetic peroxide OZ78 is effective against Echinostoma caproni and Fasciola hepatica

Response of two isolates of Fasciola hepatica to treatment with triclabendazole in vivo and in vitro

Measurement of triclabendazole and its metabolites in liver flukes: method development and full validation

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