Cambendazole and nondrug macromolecules in tissue residues

The anthelmintic cambendazole is rapidly metabolized to at least 13 urinary metabolites. Radioactivity was found in liver for weeks after a single dose in cattle, but even at 3 days' withdrawal, cambendazole and metabolites previously identified in urine accounted for only a small fraction of liver radioactivity. The radioactivity was ubiquitously distributed in protein and nucleic acid fractions, and [14C] glutamic acid was identified, indicating incorporation of 14C into the endogenous pool. Part of the residual liver radioactivity at 7 days was convertible chemically to 5-nitrobenzimidazole, indicating a drug-related macromolecular residue. However, data from rats fed radiolabeled steer liver indicate that the residue is minimally bioavailable and therefore of substantially less toxicological concern than cambendazole itself.