Albendazole and Clorsulon in Fasciola hepatica Control: Integrated Pharmacokinetic and Flukicidal Eficacy Assessment in Sheep

Abstract

Fasciola hepatica causes fasciolosis, a growing zoonotic disease that affects both livestock and humans worldwide. The main strategy to control fasciolosis in livestock animals, is 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 and its resistance is growing. The use of drug combinations has been proposed as a strategy to delay it. This study compares the pharmacokinetics and flukicidal efficacy of ABZ + CLOR when administered together or separately in sheep infected with F. hepatica. Enhanced systemic exposure of the ABZ sulphoxide metabolite was observed after the co-administration ABZ + CLOR compared to the ABZ alone treatment. The CLOR disposition kinetics was not affected by its co-administration with ABZ. The flukicidal clinical efficacy was 85% (ABZ), 92% (CLOR) and 100% (ABZ + CLOR), respectively. The work described here contributes to the characterization of the disposition kinetics of both flukicidal molecules showing that the combined ABZ and CLOR therapy may enhance the efficacy against F. hepatica in sheep.