title: Uptake of albendazole and albendazole sulphoxide by Haemonchus contortus and Fasciola hepatica in sheep.
abstract: The pattern of in vivo uptake of albendazole (ABZ) and its major metabolite, ABZ-sulphoxide (ABZSO), by Haemonchus contortus and Fasciola hepatica recovered from ABZ-treated sheep, was investigated. Concentration profiles of both compounds were simultaneously measured in target tissues/fluids from the same infected sheep. In addition, the proportion of the (+) and (-) ABZSO enantiomers was determined in plasma, bile and F. hepatica recovered from treated sheep. Sheep naturally infected with H. contortus were intraruminally (i.r.) treated with ABZ (micronized suspension, 7. 5mg/kg) and the plasma concentrations of ABZSO and ABZ-sulphone (ABZSO(2)) determined in addition to the concentration of ABZ and ABZSO in H. contortus, abomasal mucosa and fluid content samples. In addition, F. hepatica artificially infected sheep were treated i.r. with the same ABZ suspension (7.5mg/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 ABZSO. ABZSO and ABZSO(2) were the analytes recovered in plasma with ABZ and ABZSO present in H. contortus. ABZ was the analyte recovered at the highest concentration in H. contortus and abomasal mucosa, whereas higher concentrations of ABZSO were measured in abomasal fluid content. Only low concentrations of ABZ were detected in F. hepatica and bile, but markedly higher concentrations of ABZ were measured in liver tissue. ABZSO was the main molecule recovered 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.
authors.affiliation: Area Farmacología Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Campus Universitario, 7000, Tandil, Argentina.
authors.forename: L I
authors.initials: LI
authors.lastname: Alvarez
authors.forename: F A
authors.initials: FA
authors.lastname: Imperiale
authors.forename: S F
authors.initials: SF
authors.lastname: Sánchez
authors.forename: G A
authors.initials: GA
authors.lastname: Murno
authors.forename: C E
authors.initials: CE
authors.lastname: Lanusse
mesh_terms: D000018:Abomasum / Q000469:parasitology; D015766:Albendazole / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001798:Blood Proteins / Q000032:analysis; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D005210:Fasciola hepatica / Q000254:growth & development / Q000378:metabolism*; D005211:Fascioliasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D005969:Glutamate Dehydrogenase / Q000097:blood; D006188:Haemonchiasis / Q000188:drug therapy / Q000469:parasitology / Q000662:veterinary*; D006189:Haemonchus / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D012709:Serum Albumin / Q000032:analysis; D012712:Serum Globulins / Q000032:analysis; D012756:Sheep; D012757:Sheep Diseases / Q000097:blood / Q000188:drug therapy / Q000469:parasitology*; D013237:Stereoisomerism; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000871:Anthelmintics; D001798:Blood Proteins; D012709:Serum Albumin; D012712:Serum Globulins; D005969:Glutamate Dehydrogenase; D005723:gamma-Glutamyltransferase; D015766:Albendazole