Combined albendazole-clorsulon treatment to control Fasciola hepatica: integrated pharmacokinetic and efficacy evaluations in sheep

Abstract

Fasciola hepatica causes fasciolosis, a growing zoonotic disease that affects both livestock and humans worldwide. The WHO has recognized it as a significant emerging neglected disease. Anthelmintic treatments are the main strategy to control fasciolosis in livestock animals, based on drugs such as triclabendazole (TCBZ), albendazole (ABZ), clorsulon (CLOR), nitroxynil, closantel, and rafoxanide. Only TCBZ is available for F. hepatica control in human medicine. However, the intensive use of TCBZ in veterinary medicine has exerted a significant selection pressure, leading to the development of resistant populations of F. hepatica. The use of drug combinations has been proposed as a strategy to preserve efficacy and delay the development of parasite resistance. The goal of the current work was to characterize the pharmacokinetic disposition and flukicidal efficacy for the ABZ+CLOR co-administration in F. hepatica infected sheep. The pharmacokinetic(PK) study included three (3) treated experimental groups: ABZ, CLOR and ABZ+CLOR.An untreated control group was included to perform the controlled efficacy test. Fourteen(14) days after treatment, animals were sacrificed, and adult F. hepatica specimens were removed from bile ducts and counted to evaluate the efficacy. The CLOR disposition kinetics was not affected by its co-administration withABZ. Enhanced systemic exposure of the ABZsulphoxide metabolite was observed after theco-administration ABZ+CLOR compared to theABZ alone treatment. The flukicidal efficacywas 85% (ABZ), 92% (CLOR) and 100% (ABZ+-CLOR). The work described here contributes to the characterization of the disposition kineticsof both flukicidal molecules showing that the combined ABZ and CLOR therapy may enhance flukicidal efficacy in sheep.