Aspects of the pharmacokinetics of albendazole sulphoxide in sheep.

Abstract

The plasma disposition kinetics of albendazole sulphoxide (ABZSO), ((+)ABZSO and (-)ABZSO) and its sulphone metabolite (ABZSO2) were investigated in adult sheep. Six Corriedale sheep received albendazole sulphoxide by intravenous injection at 5 mg/kg live weight. Jugular blood samples were taken serially for 72 h and the plasma was analysed by high-performance liquid chromatography (HPLC) for albendazole (ABZ), ABZ sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). Albendazole was not detected in the plasma at any time after the treatment, ABZSO and ABZSO2 being the main metabolites detected between 10 min and 48 h after treatment. A biexponential plasma concentration versus time curve was observed for both ABZSO and ABZSO2 following the intravenous treatment. The plasma AUC values for ABZSO and ABZSO2 were 52.0 and 10.8 (microg x h)/ml, respectively. The ABZSO2 metabolite was measurable in plasma between 10 min and 48 h after administration of ABZSO, reaching a peak concentration of 0.38 microg/ml at 7.7 h after treatment. Using a chiral phase-based HPLC method, a biexponential plasma concentration versus time curve was observed for both ABZSO enantiomers. The total body clearance was higher for the (-) than for the (+) enantiomer, the values being 270.6 and 147.75 (ml/h)/kg, respectively. The elimination half-life of the (-) enantiomer was shorter than that of the (+) enantiomer, the values being 4.31 and 8.33 h, respectively. The enantiomeric ratio (+)ABZSO/( )ABZSO at t0 was close to unity. However, the ratio in the plasma increased with time.