RT Journal Article SR Electronic T1 Absorption, Metabolism, and Excretion of [14C]MK-0524, a Prostaglandin D2 Receptor Antagonist, in Humans JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1196 OP 1202 DO 10.1124/dmd.107.014696 VO 35 IS 7 A1 Bindhu Karanam A1 Maria Madeira A1 Scott Bradley A1 Larissa Wenning A1 Rajesh Desai A1 Eric Soli A1 David Schenk A1 Allen Jones A1 Brian Dean A1 George Doss A1 Graigory Garrett A1 Tami Crumley A1 Ajay Nirula A1 Eseng Lai YR 2007 UL http://dmd.aspetjournals.org/content/35/7/1196.abstract AB [(3R)-4-(4-Chlorobenzyl)-7-fluoro-5-(methylsulfonyl)-1,2,3,4-tetrahydrocyclopentaindol-3-yl]acetic acid (MK-0524) is a potent orally active human prostaglandin D2 receptor 1 antagonist that is currently under development for the prevention of niacin-induced flushing. The metabolism and excretion of [14C]MK-0524 in humans were investigated in six healthy human volunteers following a single p.o. dose of 40 mg (202 μCi). [14C]MK-0524 was absorbed rapidly, with plasma Cmax achieved 1 to 1.5 h postdose. The major route of excretion of radioactivity was via the feces, with 68% of the administered dose recovered in feces. Urinary excretion averaged 22% of the administered dose, for a total excretion recovery of ∼90%. The majority of the dose was excreted within 96 h following dosing. Parent compound was the primary radioactive component circulating in plasma, comprising 42 to 72% of the total radioactivity in plasma for up to 12 h. The only other radioactive component detected in plasma was M2, the acyl glucuronic acid conjugate of the parent compound. The major radioactive component in urine was M2, representing 64% of the total radioactivity. Minor metabolites included hydroxylated epimers (M1/M4) and their glucuronic acid conjugates, which occurred in the urine as urea adducts, formed presumably during storage of samples. Fecal radioactivity profiles mainly comprised the parent compound, originating from unabsorbed parent and/or hydrolyzed glucuronic acid conjugate of the parent compound. Therefore, in humans, MK-0524 was eliminated primarily via metabolism to the acyl glucuronic acid conjugate, followed by excretion of the conjugate into bile and eventually into feces. The American Society for Pharmacology and Experimental Therapeutics