Oxfendazole kinetics in pigs: In vivo assessment of its pattern of accumulation in Ascaris suum

CEBALLOS, LAURA; CANTON, CANDELA; CADENAZZI, GABRIELA; VIRKEL, GUILLERMO; DOMINGUEZ, PAULA; MORENO, LAURA; LANUSSE, CARLOS; ALVAREZ, LUIS

EXPERIMENTAL PARASITOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Año: 2019 vol. 199 p. 52 - 58

0014-4894

Ascaris suum is a widespread parasitic nematode that causes infection in pigs with high prevalence rates.Oxfendazole (OFZ) is effective against A. suum when used at a single high oral dose of 30 mg/kg. The aim of thisstudy was to assess the pattern of distribution/accumulation of OFZ and its metabolites, in bloodstream(plasma), mucosal tissue and contents from small and large intestine and adult specimens of A. suum collectedfrom infected and treated pigs. The activity of glutathione-S-transferases (GSTs) in A. suum was also investigated.Infected pigs were orally treated with OFZ (30 mg/kg) and sacrificed at 0, 3, 6 and 12 h after treatment. Samplesof blood, mucosa and contents from both small and large intestine as well as adult worms were obtained andprocessed for quantification of OFZ/metabolites by HPLC. OFZ was the main analyte measured in all of theevaluated matrixes. The highest drug concentrations were determined in small (AUC0-t 718.7 ± 283.5 μg h/g)and large (399.6 ± 110.5 μg h/g) intestinal content. Concentrations ranging from 1.35 to 2.60 μg/g (OFZ) weremeasured in adult A. suum. GSTs activity was higher after exposure to OFZ both in vivo and ex vivo. The dataobtained here suggest that the pattern of OFZ accumulation in A. suum would be more related to the concentration achieved in the fluid and mucosa of the small intestine than in other tissues/fluids. It is expected thatincrements in the amount of drug attained in the tissues/fluids of parasite location will correlate with increaseddrug concentration within the target parasite, and therefore with the resultant treatment efficacy. The results areparticularly relevant considering the potential of OFZ to be used for soil transmitted helminths (STH) controlprograms and the advantages of pigs as a model to assess drug treatment to be implemented in humans.