Triclabendazole and metabolites accumulation in liver flukes recovered from treated sheep.

CEBALLOS, L.; ALVAREZ, L.; MORENO, L.; FAIRWEATHER, I.; LANUSSE, C.

Buenos Aires

Congreso; 23 International Conference of the World Association for the Advancement of Veterinary Parasitology; 2011

AAVP

The fluckicidal compound triclabendazole (TCBZ) has a complex metabolic pattern that includes the systemic presence of sulphoxide (TCBZSO) and sulphone (TCBZSO2) derivatives, as well as the hydroxi-TCBZ metabolites usually recovered from the bile of treated animals. The aim of current work was to evaluate the pattern of in vivo TCBZ/metabolites accumulation into adult Fasciola hepatica specimens recovered from infected sheep. Twelve (12) healthy Corriedale sheep were orally infected with one hundred (100) metacercariae of a TCBZ-susceptible F.hepatica isolate. Sixteen (16) weeks after infection, animals were intraruminally treated with TCBZ (10 mg/kg). At 3, 24, 48 and 60 h post-treatment, animals were sacrificed (n= 3) and samples of blood, bile, liver tissue and adult F.hepatica specimens were collected. TCBZ/metabolites concentrations were measured by HPLC. TCBZ-sulphoxide (TCBZSO) and sulphone (TCBZSO2) were the only molecules recovered in the bloodstream with peak plasma concentration of 10.8 (TCBZSO) and 12.6 (TCBZSO2) µg/mL. The same metabolites were also the main analytes accumulated within the adult flukes, reaching peak concentrations between 6.35 (TCBZSO) and 13.9 (TCBZSO2) µg/g at 24 h post-treatment, which was coincident with the time where the maximum plasma concentration was attained. Low TCBZ concentrations (0.14 µg/g at 24 h) were measured within F.hepatica. TCBZ parent drug and its sulpho- and hydroxi-derivatives were recovered in bile collected from treated sheep between 3 and 60 h post-treatment. Although relatively high concentrations of hydroxi-TCBZ (ranging from 0.86 to 10.6 µg/mL) were measured in bile, this metabolite was not recovered within the flukes at any time post-treatment. Finally, TCBZ parent drug was the main compound accumulated in liver tissue over the 60 h post-treatment period. The drug concentration patterns observed within the adult liver fluke after TCBZ treatment followed a similar trend to those found in plasma. Overall, the data reported here confirm that the oral ingestion is a main route of drug entry into the trematode in vivo exposed to TCBZ/metabolites. However, the presence of TCBZ within the adult fluke (absent in the systemic circulation) may be related to some degree of transtegumental diffusion from bile or by a direct oral ingestion from portal blood.