FASTING-INDUCED CHANGES TO THE PHARMACOKINETIC BEHAVIOR OF ALBENDAZOLE AND ITS METABOLITES IN CALVES

The influence of fasting on the bioavailability and disposition kineti cs of albendazole (ABZ) and its metabolites in cattle was investigated . ABZ (10 mg/kg) was given by intraruminal (i.r.) (Experiment 1) and i ntravenous (i.v.) (Experiment 2) administration to Holstein calves eit her fed ad libitum (control) or subjected to a 48 h fasting period (fa sted group) prior to treatment. The rate of passage of digesta through the gastrointestinal (GI) tract was evaluated by measurement of cobal t faecal excretion following the oral administration of the sodium-cob alt-ethylendiamine-tetracetic acid complex to calves subjected to the feeding conditions above described, Jugular blood and abomasal fluid ( via cannula) samples were collected over 120 h post-treatment; samples were analysed by high performance liquid chromatography (HPLC) for AB Z, ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO(2)). Fasting the ani mals prior to the i.r. treatment resulted in pronounced modifications to the plasma and abomasal fluid disposition kinetics of ABZ and its m etabolites. A greater extent of GI absorption with significantly highe r C-max (150%) and AUC (310%) values for ABZSO in plasma, was observed in fasted compared to fed animals following the i.r. administration o f ABZ. Extended detection of ABZ metabolites resulting in significantl y longer plasma t(1/2el) and MRT was also obtained in fasted compared to fed calves. These results correlated with the substantially enhance d availability of ABZ and its metabolites (AUCs over 200% greater) in the abomasal fluid of the fasted animals. Fasting did not induce chang es to the plasma disposition of either ABZ or its metabolites after th e i.v. treatment. The digesta passage rate, measured by the amount of cobalt excreted in faeces, was significantly lower in fasted compared to animals fed ad libitum. A delayed GI transit time that decreases th e rate of passage of the drug down the digestive tract, may have accou nted for enhanced ABZ dissolution and absorption in fasted compared to fed calves. The findings reported in this article show that fasting p rior to treatment notably affects the bioavailability and disposition kinetics of ABZ and its metabolites in cattle.