IMIDOCARB DEPLETION FROM CATTLE LIVER AND MECHANISM OF RETENTION IN ISOLATED BOVINE HEPATOCYTES

Imizol injection (imidocarb) is used for the prevention and treatment of babesiosis in cattle. Studies in sheep indicate that imidocarb is r etained in edible tissues (Aliu ct al.). In the present study we have set up and validated a high-performance Liquid chromatography based me thod to investigate the retention of imidocarb in cattle liver. Imidoc arb was still detectable 224 d after a single therapeutic dose with a half-life of 42.7 d, The mechanism of imidocarb retention by bovine li ver was modelled using isolated bovine hepatocytes. Incubations with i solated hepatocytes indicated that [C-14]imidocarb binding was depende nt on hepatocyte number and showed signs of saturation. Bound [C-14]im idocarb could be eluted from hepatocytes with buffer and extracted wit h solvents. Equilibrium dialysis under denaturing conditions (Sun and Dent) indicated that 3% of the [C-14]imidocarb was covalently bound to macromolecules. Although the hepatocyte preparations demonstrated the capacity for phase I and II 7-ethoxycoumarin metabolism no metabolite s of [C-14]imidocarb were found. Further in vitro binding studies invo lving sub-cellular fractionation indicated that [C-14]imidocarb is par titioned largely in the nuclear fraction of bovine liver homogenates a nd that it binds to deoxyribonucleic acid.