A mass balance study to evaluate the biotransformation and excretion of [C-14]-triamcinolone acetonide following oral administration

The principle objective of this study was to characterize the absorption, m etabolism, and disposition of orally administered [C-14]-triamcinolone acet onide. Six healthy male subjects each received a single 100 mu Ci (approxim ate to 800 mu g) oral dose of [C-14]-triamcinolone acetonide. Plasma, urine , and fecal samples were collected at selected times and analyzed for triam cinolone acetonide and [C-14]-derived radioactivity. Plasma protein binding of triamcinolone acetonide was also determined. Metabolite profiling and i dentification were carried out in plasma and excreta. Principle metabolites were assessed for activity with in vitro anti-inflammatory models. [C-14]- triamcinolone acetonide was found to be systemically absorbed following ora l administration. The presystemic metabolism and clearance of triamcinolone acetonide were extensive, with only a small fraction of the total plasma r adioactivity being made up of triamcinolone acetonide. Little to no parent compound was detected in the plasma 24 hours after administration. Most of the urinary and fecally [C-14]-derived radioactivity was also excreted with in 24 and 72 hours postdose, respectively Mean plasma protein binding of tr iamcinolone acetonide was constant, predictable, and a relatively lo rv 68% over a 24-fold range of plasma concentrations. Three principle metabolites of triamcinolone acetonide were profiled in plasma, urine, and feces. Thes e metabolites were identified as 6 beta-hydroxy triamcinolone, al-carboxyli c acid triamcinolone acetonide, and 6 beta-hydroxy-21-oic triamcinolone ace tonide. All three metabolites failed to show any concentration-dependent ef fects in anti-inflammatory models evaluating IL-5-sustained eosinophil viab ility and IgE-induced basophil histamine release.