Triclabendazole resistant Fasciola hepatica: pharmacokinetic and efficacy assessments of a drug combined treatment

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

Buenos Aires, Argentina

Otro; Reunión anual de la Sociedad Argentina de Farmacología Experimental (SAFE); 2007

Sociedad Argentina de Farmacología Experimental

The altered drug influx/efflux and enhanced metabolic capacity identified in triclabendazole (TCBZ)-resistant Fasciola hepatica might contribute to the development of resistance to TCBZ. The aim of this work was to evaluate the pharmacokinetics (PK) and clinical efficacy (CE) of TCBZ administered alone or co-administered with ivermectin (IVM, drug efflux inhibitor) and methimazole (MTZ, metabolic inhibitor) in TCBZ-resistant F. hepatica parasitized sheep. Sheep infected with TCBZ-resistant F. hepatica were divided into three groups (n= 4): untreated control, TCBZ-treated (10 mg/kg) and TCBZ+IVM+MTZ treated sheep (10, 0.2 and 1.5 mg/kg, respectively). Plasma samples were collected (PK study) and analysed by HPLC. In the CE study, the animals were sacrificed at 15 days post-treatment to evaluate the comparative efficacy against TCBZ-resistant F. hepatica. The presence of IVM and MTZ did not affect the plasma PK behaviour of TCBZ metabolites. The combined drug treatment was not sufficient to enhance the poor efficacy of TCBZ against resistant F. hepatica. In conclusion, the higher TCBZ concentration observed in F. hepatica in presence of IVM or MTZ after ex vivo assays, were not evidenced in this in vivo trial.