THE FATE OF A THIAZOLIDINEDIONE ANTIDIABETIC AGENT IN RAT AND DOG

1. The fate of [C-14] BRL 49653C, a novel thiazolidinedione antidiabet ic agent, has been studied following oral administration to the rat an d dog. 2. Clearance was almost exclusively by metabolism, with only sm all amounts of unchanged BRL 49653 being excreted by either species. 3 . Phase I metabolism resulted in ring hydroxylation, N-demethylation a nd oxidative removal of the pyridinylamino function to yield a phenoxy acetic acid derivative. 4. Sulphation of phase I metabolites occurred in both species, but glucuronidation was only observed in the rat. 5. The parent compound was the major circulating component in both specie s at early times, but at later times sulphate conjugates of phase 1 me tabolites were predominant.