Identification of etretinate metabolites in human bile.

The metabolites of etretinate (Tegison) were investigated in bile obtained from two patients with biliary T-tubes. Bile samples were collected for 5 days after administration of a single, oral 100-mg dose of 14C-labeled etretinate. Radioactivity measurements indicated that the two patients excreted 9.6% and 8.0% of the dose in the 5-day bile. The etretinate metabolites in the bile were present mainly as beta-glucuronidase-labile conjugates. HPLC analyses of the beta-glucuronidase-treated bile samples showed no measurable concentrations (less than 10 ng/ml) of etretinate or the 13-cis acid, isoacitretin. Acitretin, the free acid of etretinate, was present and accounted for about 0.9% of the biliary radioactivity. The major portion of the radioactivity in the extracts of the beta-glucuronidase-treated bile samples consisted of two metabolites with shortened side chains. One was identified as the 11, 12-dihydro-13, 14, 15, 20-tetranor phenolic derivative of acitretin, which was previously identified as a human urinary metabolite. The other metabolite was identified as the 11, 12, 13, 14-tetrahydro-15-nor phenolic derivative of acitretin, which has not been previously identified as a metabolite of etretinate.