Excretion of Propylthiouracil and Its Metabolites in Rat Bile and Urine

Abstract

Metabolites of propylthiouracil (PTU) appearing in rat bile and urine were compared after administration of 14C-PTU or 35S-PTU. Chromatography of 24-hr urines on Bio Gel P-2 columns resulted in the separation of several peaks of radioactivity. Each peak was subjected to further study. The results demonstrated that the most abundant component of urine was unaltered PTU and confirmed that PTU-glucuronide was a major urinary metabolite. These compounds accounted for 42.3 and 16%, respectively, of the total urinary radioactivity. Three metabolites heretofore unreported in rat urine, sulfate, propyluracil (PU) and S-methyl propylthiouracil (S-rhethyl PTU), were identified and comprised 7, 5.1 and 3.5%, respectively, of the total radioactivity. The major metabo- lite (22%) was not identified but appeared to be an S-conjugate of PTU or a PTU metabolite. Several radioactive PTU metabolites were also observed i n 6-hr bile. The most abundant metabolite was PTU-glucuronide comprising 41.9% of the total with small amounts of unaltered PTU and of sulfate also being observed. Two other substances were glucuronides of unidentified PTU metabolites and 3 unidentified compounds appeared to be S-conjugates of PTU or a PTU metabolite. The variety of metabolites observed suggests that several pathways are involved in PTU metabolism in the rat and that a major site of biological alteration in the PTU molecule is the S group. (Endocrinology94: 1689, 1974)