Uptake of albendazole and albendazole sulphoxide by Haemonchus contortus and Fasciola hepatica in sheep

The pattern of in vivo uptake of albendazole (ABZ) and its major metabolite , ABZ-sulphoxide (ABZSO), by Haemonchus contortus and Fasciola hepatica rec overed from ABZ-treated sheep, was investigated. Concentration profiles of both compounds were simultaneously measured in target tissues/fluids from t he same infected sheep. In addition, the proportion of the (+) and (-) ABZS O enantiomers was determined in plasma, bile and F. hepatica recovered from treated sheep. Sheep naturally infected with H. contortus were intrarumina lly (i.r.) treated with ABZ (micronized suspension, 7.5 mg/kg) and the plas ma concentrations of ABZSO and ABZ-sulphone (ABZSO(2)) determined in additi on to the concentration of ABZ and ABZSO in H. contortus, abomasal mucosa a nd fluid content samples. In addition, f. hepatica artificially infected sh eep were treated i.r. with the same ABZ suspension (7.5 mg/kg), and samples of blood, bile, liver tissue and adult flukes were collected and analysed by HPLC to determine the concentrations of ABZ and both enantiomers of ABZS O. ABZSO and ABZSO2 were the analytes recovered in plasma with ABZ and ABZS O present in H. contortus. ABZ was the analyte recovered at the highest con centration in H. contortus and abomasal mucosa, whereas higher concentratio ns of ABZSO were measured in abomasal fluid content. Only low concentration s of ABZ were detected in F: hepatica and bile, but markedly higher concent rations of ABZ were measured in liver tissue. ABZSO was the main molecule r ecovered in F: hepatica, plasma and bile samples collected from ABZ-treated sheep. The (+) enantiomer of ABZSO was recovered at a higher proportion in plasma (75%), bile (78%) and F: hepatica (74%) after ABZ administration to infected sheep. (C) 2000 Elsevier Science B.V. All rights reserved.