TY - JOUR T1 - Absorption, Metabolism, and Excretion of [<sup>14</sup>C]MK-0767 (2-Methoxy-5-(2,4-dioxo-5-thiazolidinyl)-<em>N</em>-[[4-(trifluoromethyl)phenyl] methyl]benzamide) in Humans JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1457 LP - 1461 DO - 10.1124/dmd.106.010231 VL - 34 IS - 9 AU - Christopher J. Kochansky AU - Ronda K. Rippley AU - Kerri X. Yan AU - Hengchang Song AU - Michael A. Wallace AU - Dennis Dean AU - Allen N. Jones AU - Kenneth Lasseter AU - Jules Schwartz AU - Stella H. Vincent AU - Ronald B. Franklin AU - John Wagner Y1 - 2006/09/01 UR - http://dmd.aspetjournals.org/content/34/9/1457.abstract N2 - MK-0767 (KRP-297; 2-methoxy-5-(2,4-dioxo-5-thiazolidinyl)-N-[[4-(trifluoromethyl)phenyl] methyl]benzamide) is a thiazolidinedione (TZD)-containing dual agonist of the peroxisome proliferator-activated receptors α and γ that has been studied as a potential treatment for patients with type 2 diabetes. The metabolism and excretion of [14C]MK-0767 were evaluated in six human volunteers after a 5-mg (200 μCi) oral dose. Excretion of 14C radioactivity was found to be nearly equal into the urine (∼50%) and feces (∼40%). Elimination of [14C]MK-0767 was primarily by metabolism, with minimal excretion of parent compound into the urine (&lt;0.5% of dose) and feces (∼14% of the dose). [14C]MK-0767 was the major circulating compound-related entity (&gt;96% of radioactivity) through 48 h postdose. It was also found that ∼91% of the total radioactivity area under the curve was due to intact MK-0767. Several minor metabolites were detected in plasma (&lt;1% of radioactivity, each), formed by cleavage of the TZD ring and subsequent S-methylation and oxidation. All the metabolites excreted into urine were formed by TZD cleavage, whereas the major metabolite in feces was the O-demethylated derivative of MK-0767. The American Society for Pharmacology and Experimental Therapeutics ER -