title: In vivo and ex vivo uptake of albendazole and its sulphoxide metabolite by cestode parasites: relationship with their kinetic behaviour in sheep.
abstract: The current experiments correlate the disposition kinetics of albendazole (ABZ) following its intravenous (i.v.) and intraruminal (i.r.) administrations to Moniezia spp.-infected sheep, with the pattern of drug/metabolite uptake by tapeworms collected from treated animals. The ex vivo uptake pattern of ABZ and albendazole sulphoxide (ABZSO) by the same cestode parasite was also investigated. Naturally infected (Moniezia spp.) Corriedale lambs were treated with ABZ by either i.v. (Group A, n = 15) or i.r. (Group B, n = 15) administration at 7.5 mg/kg. Plasma and abomasal fluid samples were obtained over a 120-h period. Two animals per group were killed at 0.5, 1, 2, 4 and 6 h post-treatment; parasite material (tapeworms), bile and intestinal fluid samples were recovered. Furthermore, Moniezia spp. tapeworms obtained from sheep killed at the local abattoir were incubated with either ABZ or ABZSO for different time periods in a Kreb's Ringer Tris buffer (ex vivo experiments). Samples were analysed by high performance liquid chromatography for ABZ, ABZSO and albendazole sulphone (ABZSO2). ABZ plasma concentrations decreased rapidly and were not detectable beyond 10 h following i.v. administration. ABZSO and ABZSO2 were the metabolites recovered in plasma after both treatments. ABZ and its metabolites were extensively distributed to the digestive tract, mainly into the abomasal fluid, after the i.v. and i.r. administrations. The parent drug and its active ABZSO metabolite were recovered in tapeworms collected from both i.v. and i.r. treated lambs. However, the availability of both ABZ and ABZSO was higher in parasite material recovered from i.v. treated animals. The uptake of ABZ by the cestode parasite, both in vivo and ex vivo, was significantly greater than that of its sulphoxide metabolite, which agrees with the higher lipophilicity of the parent drug.
authors.affiliation: Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Tandil, Argentina.
authors.forename: L I
authors.initials: LI
authors.lastname: Alvarez
authors.forename: S F
authors.initials: SF
authors.lastname: Sánchez
authors.forename: C E
authors.initials: CE
authors.lastname: Lanusse
mesh_terms: D000018:Abomasum / Q000378:metabolism; D015766:Albendazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000465:Algorithms; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D002589:Cestoda / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D012756:Sheep / Q000378:metabolism* / Q000469:parasitology*; D013454:Sulfoxides / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000871:Anthelmintics; D013454:Sulfoxides; D015766:Albendazole