Abstract
The metabolic fate of a new thienodiazepine derivative, 1-methyl-5-o-chlorophenyl-7-ethyl-1, 2-dihydro-3H-thieno [2, 3-e] [1, 4] diazepin-2-one (Y-6047), was investigated in the rats utilizing Y-6047 labeled with 35S. When this radioactive compound (35S-Y-6047) was orally or intraperitoneally administered, approximately 50% of the given radioactivity (35S) was excreted in the urine, most of the others in the feces, during 3 days, and 71% of the given 35S was also excreted in the bile during 24 hr after oral administration. The highest concentration of 35S in organs was found 0.5-1 hr after its oral administration. A high concentration of 35S was present in the liver, kidney, and adrenals, and relatively low levels in the brain, peripheral fat, testes, and other tissues. Approximately 40-60% of 35S in the serum was bound with serum protein. The monool and diol derivatives hydroxylated at β-position or α, β-positions of 7-ethyl group of Y-6047 were identified as the urinary metabolites of Y-6047 from their spectral data. However, all of the N1-desmethyl, 3- or 5-phenyl hydroxy derivatives of Y-6047 and their glucuronides or sulfates, as well as the parent compound, could not be detected in the urine of drug-fed rats.
