title: Absorption, metabolism, and excretion of [14C]MK-0767 (2-methoxy-5-(2,4-dioxo-5-thiazolidinyl)-N-[[4-(trifluoromethyl)phenyl] methyl]benzamide) in humans.
abstract: 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 alpha and gamma 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 microCi) oral dose. Excretion of 14C radioactivity was found to be nearly equal into the urine (approximately 50%) and feces (approximately 40%). Elimination of [14C]MK-0767 was primarily by metabolism, with minimal excretion of parent compound into the urine (<0.5% of dose) and feces (approximately 14% of the dose). [14C]MK-0767 was the major circulating compound-related entity (>96% of radioactivity) through 48 h postdose. It was also found that approximately 91% of the total radioactivity area under the curve was due to intact MK-0767. Several minor metabolites were detected in plasma (<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.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, PA 19486, USA. christopher_kochansky@merck.com
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kochansky
authors.forename: Ronda K
authors.initials: RK
authors.lastname: Rippley
authors.forename: Kerri X
authors.initials: KX
authors.lastname: Yan
authors.forename: Hengchang
authors.initials: H
authors.lastname: Song
authors.forename: Michael A
authors.initials: MA
authors.lastname: Wallace
authors.forename: Dennis
authors.initials: D
authors.lastname: Dean
authors.forename: Allen N
authors.initials: AN
authors.lastname: Jones
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lasseter
authors.forename: Jules
authors.initials: J
authors.lastname: Schwartz
authors.forename: Stella H
authors.initials: SH
authors.lastname: Vincent
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Franklin
authors.forename: John
authors.initials: J
authors.lastname: Wagner
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001711:Biotransformation; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D008297:Male; D008875:Middle Aged; D013844:Thiazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D002250:Carbon Radioisotopes; D007004:Hypoglycemic Agents; C487303:MK0767; D013844:Thiazoles