RT Journal Article
SR Electronic
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
FD American Society for Pharmacology and Experimental Therapeutics
SP 1457
OP 1461
DO 10.1124/dmd.106.010231
VO 34
IS 9
A1 Christopher J. Kochansky
A1 Ronda K. Rippley
A1 Kerri X. Yan
A1 Hengchang Song
A1 Michael A. Wallace
A1 Dennis Dean
A1 Allen N. Jones
A1 Kenneth Lasseter
A1 Jules Schwartz
A1 Stella H. Vincent
A1 Ronald B. Franklin
A1 John Wagner
YR 2006
UL http://dmd.aspetjournals.org/content/34/9/1457.abstract
AB 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