Preliminary kinetic data on flubendazole formulated as a hydroxypropyl-â-cyclodextrin aqueous solution for use in sheep

CEBALLOS, L; ALVAREZ, L; SANCHEZ BRUNI, S; MORENO, L; LANUSSE, C

Córdoba. Argentina

Congreso; XXXVIII Reunion Anual de la Asociación Argentina de Farmacología Experimantal; 2006

Flubendazole (FLBZ), anthelmintic compound, has been shown a high distribution volume in sheep. Cyclodextrins (CDs) are used to enhance solubility of poor hydrosoluble compounds. The aim of this work was to compare the PK behaviour of FLBZ and its metabolites after its intraruminally (i.r) administration to sheep as a CD-solution or conventional suspension. In a Phase I of a crossover study, six male Corriedale sheep received either a CD-FLBZ solution (HPâCD 10%, FLBZ 2%) (Group 1, n= 3) or a carboximethylcellulose (CMC)-FLBZ suspension (CMC 0.5%, FLBZ 2%) (Group 2, n= 3) at the same dose (3.8 mg/kg). After a 21-days washout period treatment were reversed and the study repeated as Phase II. Blood samples were collected between 0 and 72 h post-treatment and analysed by HPLC. The administration of FLBZ as a CDs-solution in sheep (AUC=1.83± 0.12) did not induced a relevant enhancement on the plasma availability of FLBZ parent drug/metabolites compared to the CMC-suspension (AUC=1.53±0.40). It is likely that the CD-FLBZ complex, is hydrolised by the ruminal microflora-mediated metabolic process.