Abstract
Absorption, excretion and metabolism of d-cis-3-acetoxy-5-[2-(dimethylamino) ethyl]-2, 3-dihydro-2-(p-methoxyphenyl)-1, 5-benzothiazepin-4 (5H)-one hydrochloride (CRD-401) were studied in rats. CRD-401 was found to be absorbed rapidly and almost completelyfrom the digestive tract, the half-life for absorption being 26 min.
More than 90% of the radioactivity after oral administration of 14C-CRD-401 wasrecovered from the feces and urine within 72 hours. The feces is the major excretoryroute since approximately 60% of the total radioactivity recovered appeared in the 72hour feces and 65% of the administrated radioactivity was excreted in the 24 hour bile.
CRD-401 was extensively metabolized by rat since only 0.1% of the drug wasrecovered unchanged in the 24 hour urine and bile. Metabolic pathways of CRD-401 consisted of deacetylation, N-demethylation, O-demethylation, hydroxylation andN-oxidation. Major metabolites in urine and bile were deacetyl-O-demethyl-CRD-401, deacetyl-N, O-demethyl-CRD-401, and deacetyl-N, O-demetyl-methoxyl-CRD-401. Thepresence of N-oxide analogs of CRD-401 as minor metabolites was demonstrated inurine but not in bile.
