Exogenous Iron Increases Fasciocidal Activity and Hepatocellular Toxicity of the Synthetic Endoperoxides OZ78 and MT04.

The synthetic peroxides OZ78 and MT04 recently emerged as fasciocidal drug candidates. However, the effect of iron on fasciocidal activity and hepatocellular toxicity of these compounds is unknown. We investigated the in vitro fasciocidal activity and hepatocellular toxicity of OZ78 and MT04 in absence and presence of Fe(II)chloride and hemin, and conducted a toxicological study in mice.

Isothermal microcalorimetry to study the activity of triclabendazole and its metabolites on juvenile and adult Fasciola hepatica.

Isothermal microcalorimetry (IMC) is an analytical tool that continuously measures the heat flow generated by chemical, physical or biological processes. We have demonstrated that IMC is a useful tool to analyze drug effects on helminths, including adult Fasciola hepatica. Here, we used IMC to examine the activity of triclabendazole and its metabolites triclabendazole sulphone and triclabendazole sulphoxide on juvenile and adult F.

Pharmacokinetics of the fasciocidal drug candidates MT04 and OZ78 in uninfected rats and in vitro pharmacodynamic studies.

OZ78 and MT04 are promising drug candidates against fascioliasis (fasciolosis). We determined basic pharmacokinetic (PK) parameters of OZ78 and MT04 in uninfected rats. Rats were treated with single oral doses of 50 mg/kg OZ78 or MT04.

Activity of OZ78 analogues against Fasciola hepatica and Echinostoma caproni.

The rapid spread of triclabendazole resistance in veterinary medicine is an important motivation for the discovery and development of novel fasciocidal drugs. The aim of this study was to characterize the fasciocidal properties of 1,2,4,5-tetraoxane (MT04 and MT14) and 1,2,4-trioxane (ST16 and ST28) analogues of the fasciocidal drug candidate OZ78, a 1,2,4-trioxolane. Dose response relationships were determined against juvenile and adult Fasciola hepatica in rats and Echinostoma caproni in mice.

Development and validation of a liquid chromatography/mass spectrometry method for pharmacokinetic studies of OZ78, a fasciocidal drug candidate.

Fascioliasis is a zoonotic disease of considerable public health and great veterinary significance and new drugs are needed. OZ78 is a promising fasciocidal drug candidate. In order to support the development of OZ78, including pharmacokinetic (PK) studies an accurate, precise, and selective liquid chromatography/mass spectrometry (LC/MS) method for OZ78 was developed for sheep plasma and validated in accordance with the US Food and Drug Administration Guidance on Bioanalytical Method Validation.

Efficacy, safety and pharmacokinetics of 1,2,4-trioxolane OZ78 against an experimental infection with Fasciola hepatica in sheep.

The synthetic peroxide OZ78 is an effective flukicide in the rodent model, but the potential of OZ78 in target animals has not been studied to date. In the present study, OZ78 was administered at 50mg/kg orally and subcutaneously to sheep harbouring an experimental Fasciola hepatica infection and the efficacy, tolerability and pharmacokinetic profiles were monitored. OZ78 given orally or subcutaneously revealed no effect neither on faecal egg counts nor on worm burdens.