Repurposing oxfendazole as a potential flukicidal compound

CEBALLOS, LAURA; CANTÓN, CANDELA; DOMINGUEZ, PAULA; MORENO, LAURA; GALLO, VALERIA; LANUSSE, CARLOS EDMUNDO; ALVAREZ, LUIS IGNACIO

Utah

Congreso; AAVP 65th Annual Conference; 2020

American Association of Veterinary Parasitologists

Oxfendazole (OFZ) is a nematodicidal drug without flukicidal activity at its recommendedtherapeutic dose in sheep (5 mg/kg). However, flukicidal activity has been described when OFZwas used at a higher dose (30 mg/kg) both in sheep and pigs. The goals of this study were tocharacterize the OFZ/metabolites plasma disposition kinetics after OFZ administration at either 5(OFZ5) or 30 (OFZ30) mg/kg dose to non-infected sheep (PK study), and to evaluate the doserelatedpattern of in vivo accumulation of OFZ/metabolites into F. hepatica (Accumulationstudy). Pk study: sheep (n=12) were orally treated with OFZ at either 5 (OFZTD) or 30 (OFZ30)mg/kg. Blood samples were collected over 96 h p.t. Accumulation study: F. hepatica infectedanimals (n=8) were orally treated with OFZ at either 5 or 30mg/kg. Animals were sacrificed bycaptive bolt in accordance with the Animal Welfare Policy (Act 087/02) of the Faculty ofVeterinary Medicine, UNCPBA, Tandil, Argentina and internationally accepted animal welfareguidelines (AVMA, 2001). After sacrifice, samples of blood, bile, liver and adult liver flukeswere obtained at different times. OFZ was the main analyte detected in plasma from OFZ treatedsheep and its systemic exposure (AUC0?LOQ) increased from 17.9 ± 3.71 (OFZ5) up to 85.4 ±22.6 (OFZ30) μg.h/mL. The Cmax value was 4-fold higher in the OFZ30 group than that in OFZ5group. These differences were also reflected in the pattern of OFZ accumulation into F. hepatica,which was 332 % higher in group OFZ30 (4.28 μg/g) than OFZ5 (0.99 μg/g). The OFZ doseincrement was clearly associated with a higher plasma drug exposure and accumulation into theF. hepatica, which help to explain the OFZ flukicidal efficacy observed after a dose of 30 mg/kg.The reported pharmacological data may contribute to assess OFZ repurposing for a new use asflukicidal.