The pharmacokinetics of albendazole metabolites following administration of albendazole, albendazole sulfoxide and netobimin to one-month- and eight-month-old sheep

Abstract

The principal metabolites detected in plasma of sheep following oral administration of albendazole (ABZ), albendazole sulfoxide (ABSO) and netobimin (NTB) each at 5.0 mg kg-1 body weight were ABSO and albendazole sulfone (ABSO2). The areas under the plasma concentration-time curve (AUC) for ABSO and ABSO2 were significantly (P <0.05) larger following administration for ABSO than NTB in 1-month- and 8-month-old sheep. The AUC for the ABSO and ABSO2 metabolites were larger following administration of ABZ than NTB in 1-month- but not 8-month-old sheep and the AUC of the ABSO and ABSO2 metabolites were greater following ABSO than ABZ as parent compound in 8-month-old sheep only. The larger AUC values for metabolites following administration of ABSO as the parent compound were generally coincident with significantly higher maximum (Cmax) concentrations and not with persistence in the body, since mean residence times (MRT) of the metabolites were not significantly different from those determined following ABZ and NTB as parent compounds. The lower metabolite concentration following administration of NTB may have been a feature of its requirement for metabolic conversion and its larger molecular weight. Correction of AUC values for molecular weight removed any significant differences between AUC values for either metabolite in 8-month-old lambs. The corrected metabolite AUCs following NTB were, however, significantly lower than those following ABSO administration in 1-month-old lambs, suggesting that immature metabolic processes in these animals contributed to the lower relative bioavailability of NTB in this age group. Age did not affect the disposition of metabolites following ABZ or ABSO but the AUC of the ABSO metabolite following NTB was significantly (P = 0.014) lower in 1-month- than in 8-month-old sheep.