Differential exposure of Haemonchus contortus to albendazole according to the site of worm location in the abomasum of infected sheep

ALVAREZ, L; SUAREZ, G; CEBALLOS, L; MORENO, L; LANUSSE, C

Congreso; 22sh International Conference of the World Association for the Advancement of Veterinary Parasitology; 2011

The relationship between drug kinetic behavior and anthelmintic activity has been extensively studied. However, there is a need to further understand how the active drug reaches target parasites of different tissue location. The trial described here was designed to measure the accumulation (drug exposure) of albendazole (ABZ) and its active metabolite, ABZ-sulphoxide (ABZSO), in Haemonchus contortus recovered from two different locations within the abomasum.  Drug measurement was carried out in worms attached to the abomasal mucosa and in those unattached “free” worms recovered from the luminal abomasal content. The data on drug accumulation within the target H. contortus was complemented with the assessment of ABZ/metabolites concentration profiles in plasma, abomasal fluid and mucosal tissue collected from the same infected lambs. Eight (8) lambs artificially infected with a benzimidazole–resistant H.contortus strain were divided into two experimental groups (n=4), and intraruminally treated with ABZ at either 5 mg/kg (ABZ5 group) or 15 mg/kg (ABZ15 group) dose rates. Animals were sacrificed at 12 h post-treatment and plasma, abomasal fluid and abomasal mucosa samples collected. Similarly, adult specimens of H.contortus from both abomasal locations (attached to mucosal tissue or unattached worms) were recovered from both experimental groups. ABZ/ABZSO concentrations were measured by HPLC. The highest ABZ concentration profiles were recovered from the abomasal mucosa, ranging from 4.7 (ABZ5) and 7.9 (ABZ15) µg/g. Conversely, the highest concentration of the more polar ABZSO metabolite was measured in the abomasal fluid content, reaching values of 2.6 (ABZ5) and 3.7 (ABZ15) µg/mL. Interestingly enough, significantly higher (P<0.05) ABZ and ABZSO accumulations were observed in H.contortus recovered from the abomasal fluid content, compared to those measured in resistant worms attached to the abomasal mucosa. ABZSO concentration profiles in unattached worms were between 177 (ABZ15) and 222 % (ABZ5) higher than those measured in worms attached to the mucosal tissue. A favourable partitioning process between worm/fluid compared to that obtained for the worm/mucosa, may have facilitated the greater drug accumulation observed in unattached worms collected from the abomasal fluid. The observed differential pattern of drug exposure according to worm location within the abomasum, may have marked influence on the survival of resistant parasites after ABZ treatment.