Imidocarb dipropionate, formulated as
Imizol, is used for the treatment and prophylaxis of bovine
babesiosis. Several studies have shown that
imidocarb remains detectable in edible ovine and bovine tissues for several months after dosing but the mechanism of retention remains unknown. In this study, the mechanism of
imidocarb retention was investigated by measuring the binding of [14C]
imidocarb to bovine hepatocytes, erythrocytes, sub-cellular fractions and isolated bovine macromolecules. The proportion of [14C]
imidocarb (10 microM) bound to cells in
suspension culture (1 x 10(7) cells.ml-1) was found to be substantially greater to hepatocytes (56.5%) than to erythrocytes (4.6%). Studies with washed erythrocytes reconstituted in plasma indicated that approximately 70% of the [14C]
imidocarb was bound to
plasma proteins, 10% to erythrocytes, and 20% remained free. Measurement of [14C]
imidocarb binding to sub-cellular fractions prepared from bovine liver revealed preferential accumulation in the nuclear, rather than in the mitochondrial, microsomal or cytosolic fractions. Binding capacities of selected bovine macromolecules for [14C]
imidocarb were in the order deoxy-
ribonucleic acid (
DNA) =
ribonucleic acid (
RNA) > >
alpha 1-acid glycoprotein (AGP) >
serum albumin (BSA) > haemoglobin (Hb).
DNA binding sites for
imidocarb remained unsaturated over the concentration range 0-100 microM [14C]
imidocarb. Competitive binding studies between
imidocarb and
pentamidine or
spermidine provided evidence for common
DNA binding sites. These studies indicated that preferential binding of [14C]
imidocarb to hepatocytes compared with erythrocytes observed in vitro was a result of substantial reversible binding to
nucleic acids and that the same cellular mechanism may be implicated in the slow elimination of
imidocarb from edible tissues in vivo.