Closantel pharmacology: pattern of drug accumulation in adult Fasciola hepatica recovered from treated sheep

CEBALLOS L1, CANTON C1, MORENO L1, FAIRWEATHER I2, LANUSSE C1, ALVAREZ L1

Liverpool

Congreso; Congreso Mundial de la World Association of Veterinary Parasitology; 2015

World Association for the Advancement of Veterinary Parasitology

Closantel (CLO) is a salicylanilide antiparasitic compound highly effective for the treatment of adult flukes, which may be formulated for oral or subcutaneous administration in ruminant species. CLO binds strongly (greater than 99.9%) and almost exclusively to plasma albumin, is poorly biotransformed and has limited distribution to tissues. Trans-tegumental diffusion and oral ingestion are the two potential routes available for drug entry into F. hepatica. Since adult liver flukes are blood-consuming parasites, plasma protein binding may have an important role in drug accumulation into the target parasite by oral ingestion. Therefore, the fluke could be potentially exposed to high drug levels in the bile (surrounding medium). The aim of the current work was to evaluate the in vivo time-course and patterns of CLO accumulation in adult F. hepatica specimens recovered from infected sheep over a 36-h post-treatment time period. Fourteen (14) adult sheep were infected with a susceptible isolate of F. hepatica metacercariae. Sixteen (16) weeks after infection, animals were treated with CLO by the oral (n=6, 10 mg/kg) or subcutaneous (n=6, 5 mg/kg) routes. At 12, 24 and 36 h post-treatment, animals were sacrificed (n= 2) and samples of blood, bile and adult F. hepatica specimens were collected. CLO concentrations were measured by HPLC. CLO peak plasma concentration after the oral (57.2 ± 4.1 µg/mL) and subcutaneous (40.3 ± 3.7 µg/mL) treatments were achieved at 36 h post-treatment. Similar CLO concentration vs time patterns were observed in the bloodstream and in the collected F. hepatica. Peak CLO concentrations within the adult flukes were 33.8 ± 11.8 (oral) and 22.8 ± 12.5 (subcutaneous) µg/g at 36 h post-treatment. Low CLO concentrations (≤2 µg/ml) were recovered in bile. Overall, the disposition kinetics and parasite accumulation data reported here confirm that the oral ingestion is a main route of drug entry into the flukes in vivo exposed to CLO.