Influence on the antithyroid compound methimazole on the plasma disposition of fenbendazole and oxfendazole in sheep

Lanusse, Carlos; Gascon, L. H.; Prichard, R. K.

doi:10.1016/0034-5288(95)90106-x

Cited by 23 publications

(18 citation statements)

References 15 publications

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“…The potentiation of drug availability observed has lead a number of workers to propose the use of such drug combinations as a strategy to deal with drug resistance (Lanusse and Prichard 1993;Lanusse et al 1995;Benchaoui and McKellar 1996;Dupuy et al 2003;Sánchez-Bruni et al 2005;Alvinerie et al 2008;Wisedpanichkij et al 2009). …”

Section: Discussionmentioning

confidence: 96%

Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

et al. 2010

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A study has been carried out to investigate whether the action of triclabendazole (TCBZ) is altered by using the metabolic inhibitor, ketoconazole (KTZ) to inhibit the cytochrome P450 (CYP 450) system within Fasciola hepatica. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 enzyme system was inhibited by a 2 h pre-incubation in KTZ (40 microM). Flukes were then incubated for a further 22 h in NCTC medium containing either KTZ; KTZ + nicotinamide adenine dinucleotide phosphate (NADPH; 1 nM); KTZ + NADPH + TCBZ (15 microg/ml); or KTZ + NADPH + triclabendazole sulphoxide (TCBZ.SO;15 microg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible isolate than the TCBZ-resistant isolate. However, co-incubation with KTZ and TCBZ/TCBZ.SO led to more severe surface changes to the TCBZ-resistant isolate than with each drug on its own, with greater swelling and blebbing of the tegument and even the loss of the apical plasma membrane in places. With the Cullompton isolate, there was limited potentiation of drug action in combination with KTZ, and only with TCBZ.SO. The results support the concept of altered drug metabolism within TCBZ-resistant isolates and indicate that this process may play a role in the development of drug resistance.

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Section: Discussionmentioning

confidence: 96%

Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

et al. 2010

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“…FMO pathways play a major role in the metabolism of xenobiotic drugs by livestock (Lanusse and Prichard 1993). The coadministration of MTZ with benzimidazole compounds in livestock has been shown to enhance the efficacy of the anthelmintic drugs, by enhancing their bioavailability via manipulation of their pharmacokinetics Prichard 1992a, b, 1993;Lanusse et al 1992Lanusse et al , 1995. The strategy has been extended to TCBZ use in sheep (Virkel et al 2006(Virkel et al , 2009.…”

Section: Discussionmentioning

confidence: 98%

Potentiation of triclabendazole sulphoxide-induced tegumental disruption by methimazole in a triclabendazole-resistant isolate of Fasciola hepatica

et al. 2010

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A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The flavin monooxygenase system (FMO) was inhibited using methimazole (MTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The FMO system was inhibited by a 2-h pre-incubation in methimazole (100 microM), then incubated for a further 22 h in NCTC medium containing either MTZ; MTZ+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nM); MTZ+NADPH+TCBZ (15 microg/ml); or MTZ+NADPH+triclabendazole sulphoxide (TCBZ.SO) (15 microg/ml). Changes to fluke ultrastructure following drug treatment and metabolic inhibition were assessed using transmission electron microscopy. After treatment with either TCBZ or TCBZ.SO on their own, there was greater disruption to the TCBZ-susceptible than triclabedazole-resistant isolate. However, co-incubation with MTZ+TCBZ, but more particularly MTZ+TCBZ.SO, led to more severe changes to the TCBZ-resistant isolate than with each drug on its own, with severe swelling of the basal infolds and mucopolysaccharide masses in the syncytium, accompanied by a reduction in numbers of secretory bodies. The synthesis and production of secretory bodies in the tegumental cells was severely affected as well. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action. The results support the concept of altered drug metabolism in TCBZ-resistant flukes, and this process may play a role in the development of drug resistance.

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“…The strategy of using anthelmintic + metabolic inhibitor combinations to deal with drug resistance has been advocated by several authors (Lanusse and Prichard, 1993;Lanusse et al, 1995;Benchaoui and McKellar, 1996;Dupuy et al, 2003;Sánchez-Bruni et al, 2005;Alvinerie et al, 2008). Moreover, greater efficacy with benzimidazole + inhibitor combinations has been demonstrated in a number of studies (Benchaoui and McKellar, 1996;López-García et al, 1998;Sánchez-Bruni et al, 2005).…”

Section: Use Of Drug Combinationsmentioning

confidence: 93%

Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?

Fairweather

2011

Veterinary Parasitology

136

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Influence on the antithyroid compound methimazole on the plasma disposition of fenbendazole and oxfendazole in sheep

Cited by 23 publications

References 15 publications

Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

Potentiation of triclabendazole sulphoxide-induced tegumental disruption by methimazole in a triclabendazole-resistant isolate of Fasciola hepatica

Reducing the future threat from (liver) fluke: realistic prospect or quixotic fantasy?

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