NUTRITIONAL CONDITION AFFECTS THE DISPOSITION KINETICS OF ALBENDAZOLEIN CATTLE

1. The influence of nutritional status on the plasma and abomasal flui d disposition kinetics of albendazole (ABZ) and its metabolites, alben dazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO(2)), has bee n investigated in the calf. 2. Free fatty acid (FFA) and beta-hydroxyb utyrate (beta-OHB) serum concentrations were significantly higher in t he feed-restricted (poor nutritional status) compared with control cal f (optimal nutritional status). 3. ABZ parent drug was not detected in plasma at any time post-treatment and ABZSO and 4BZSO(2) were the met abolites detected in plasma. Both metabolites were rapidly depleted fr om the bloodstream ABZ and its metabolites were recovered in abomasal fluid from 0.25 up to either 48 (ABZ) or 120h (ABZSO and ABZSO(2)) pos t-treatment. 4. The plasma disposition kinetics of both ABZ metabolite s was significantly changed in the feed-restricted compared with contr ol calf. ABZSO and ABZSO(2) plasma area under the curves (AUCs) were s ignificantly higher in the restricted animal. These enhanced AUCs corr elated with significantly longer plasma half-lives (T-1/2el) and mean residence times (MRTs) for these metabolites. 5. The delayed eliminati on of ABZ metabolites from the bloodstream correlated with the higher concentration of these molecules recovered in the abomasal fluid of th e calves subjected to a dietary restriction. 6. The changes observed o n disposition kinetics may reflect an impairment on the hepatic metabo lism and clearance of ABZ as a consequence of FFA mobilization from ad ipose tissue and overproduction of ketone bodies in the liver.