The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant Fasciola hepatica

Abstract

Benzimidazole anthelmintics are widely used against nematode, cestode and trematode parasites. The drugs undergo several enzyme-mediated reactions within the host animal that produce a number of metabolites. Although it has been shown that certain helminths, including Fasciola hepatica, can metabolise albendazole, nothing is known regarding the ability of the liver fluke to metabolise triclabendazole, which is the major flukicidal compound currently on the market. In the current study, adult triclabendazole-susceptible flukes were treated with triclabendazole sulphoxide in vitro, and the metabolism of the drug was monitored by high performance liquid chromatography. The data show that F. hepatica can metabolise triclabendazole sulphoxide into its relatively inert sulphone metabolite. Parallel experiments using triclabendazole-resistant flukes showed that the conversion of triclabendazole sulphoxide to triclabendazole sulphone was on average 20.29% greater in the resistant flukes compared with the susceptible flukes. The results are discussed with regard to the mechanism of triclabendazole resistance in F. hepatica.