The disposition of albendazole in sheep.

Albendazole (ABZ) was administered intraruminally at 4.75 mg/kg to sheep fitted with a permanent bile-duct cannula to determine if its metabolites might contribute to its flukicidal action. ABZ metabolism was consistent with first-pass clearance by the liver, resulting in ABZ sulphoxide (ABZ-SO) and ABZ sulphone (ABZ-SO2) being present in plasma at maximum concentrations (mean Cmax +/- SD) of 2.0 +/- 0.2 micrograms/ml and 0.4 +/- 0.1 micrograms/ml after 8 +/- 3 h and 24 +/- 5 h, respectively. ABZ-SO, but more particularly ABZ-SO2, appeared to bind to plasma proteins but their clearance rates from plasma were similar. Biliary ABZ metabolites were mainly unconjugated ABZ-SO and 2OH-ABZ-SO (8.0% dose) or conjugated glucuronide and sulphate esters (6.3% dose) mainly of 2OH-ABZ-SO and 2OH-ABZ-SO2. The concentration of the major biliary metabolite, unconjugated ABZ-SO, followed a similar time profile to that of ABZ-SO in plasma except that Cmax was much higher (6.2 +/- 2.2 micrograms/ml). Intraruminal administration of ABZ reduced bile flow rate by 30% which may be attributable to an inhibitory effect of ABZ on microtubule formation in hepatic secretory cells. It is suggested that ABZ is sequestered in the liver. This is unlikely to contribute to its flukicidal action, which is probably attributable to ingestion of ABZ-SO from bile and blood by the fluke.