title: Enhanced plasma availability of the metabolites of albendazole in fasted adult sheep.
abstract: The influence of fasting prior to treatment and of dosing rate on the plasma availability and disposition kinetics of albendazole (ABZ) and its sulphoxide (ABZSO) and sulphone (ABZSO2) metabolites was studied in adult sheep grazing on pasture. A micronized suspension of ABZ was administered orally at either 7.5 mg/kg (group A) or 11.3 mg/kg (group C) to sheep fed ad libitum, and at 7.5 mg/kg to sheep subjected to a 24 h fasting period prior to treatment (group B). Blood samples were taken serially over 96 h after treatment, and the plasma was analysed for ABZ and its metabolites by high-performance liquid chromatography. ABZSO and ABZSO2 were recovered from the plasma. Fasting induced marked modifications in the pharmacokinetic behaviour of the ABZ metabolites in sheep. An extended absorption process, with a delayed peak concentration in the plasma, was observed for both metabolites in the fasted sheep. Significantly higher area under the curve (AUC) and peak plasma concentration (Cmax) values were obtained for both metabolites in the fasted animals compared to those fed ad libitum. Delayed elimination with prolonged detection in plasma was also observed in the fasted sheep. Treatment with ABZ at 7.5 mg/kg in the starved animals resulted in bioequivalence to the administration of the compound at a 50% higher dose rate (11.3 mg/kg) in the fed animals. It is suggested that fasting enhances ABZ dissolution and absorption by delaying its passage down the digestive tract.
authors.affiliation: Departamento de Fisiopatología, Facultad de Ciencias Veterinarias, Universidad Nacional del Centro, Tandil, Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Lifschitz
authors.forename: G
authors.initials: G
authors.lastname: Virkel
authors.forename: M
authors.initials: M
authors.lastname: Mastromarino
authors.forename: C
authors.initials: C
authors.lastname: Lanusse
mesh_terms: D015766:Albendazole / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D000818:Animals; D000871:Anthelmintics / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000662:veterinary; D005215:Fasting / Q000097:blood* / Q000378:metabolism; D005260:Female; D011897:Random Allocation; D012756:Sheep / Q000097:blood* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000871:Anthelmintics; C027187:albendazole sulfone; D015766:Albendazole; C027186:albendazole sulfoxide