RT Journal Article SR Electronic T1 Disposition of a Specific Cyclooxygenase-2 Inhibitor, Valdecoxib, in Human JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 1013 OP 1021 DO 10.1124/dmd.30.9.1013 VO 30 IS 9 A1 Josh J. Yuan A1 Dai-chang Yang A1 Ji Y. Zhang A1 Roy Bible, Jr. A1 Aziz Karim A1 John W. A. Findlay YR 2002 UL http://dmd.aspetjournals.org/content/30/9/1013.abstract AB Valdecoxib is a potent and specific inhibitor of cyclooxygenase-2, which is used for the treatment of rheumatoid arthritis, osteoarthritis, and the dysmenorrhea pain. Eight male human subjects each received a single 50-mg oral dose of [14C]valdecoxib. Urine, feces, and blood samples were collected after administration of the radioactive dose. Most of the radioactivity in plasma was associated with valdecoxib and the hydroxylated metabolite of valdecoxib (M1). The estimated terminal half-life for valdecoxib was about 7 h. About 76.1% of the radioactive dose was recovered in urine and 18% of the radioactive dose was recovered in feces. Valdecoxib was extensively metabolized in human, and nine phase I metabolites were identified. The primary oxidative metabolic pathways of valdecoxib involved hydroxylation at either the methyl group to form M1 or N-hydroxylation at the sulfonamide moiety to form M2. Further oxidation of M1 led to the formation of several other phase I metabolites. Oxidative breakdown of the N-hydroxy sulfonamide function group in M2 led to the formation of corresponding sulfinic acid and sulfonic acid metabolites. The O-glucuronide conjugate of M1 andN-glucuronide conjugate of valdecoxib were the major urinary metabolites, which accounted for 23.3 and 19.5% of the total administered dose, respectively. The remaining urinary metabolites were glucuronide conjugates of other phase I metabolites. Only 3% of the administered dose was recovered in urine as unchanged parent, suggesting that renal clearance is insignificant for valdecoxib. Absorption of valdecoxib was excellent since the recovery of unchanged valdecoxib in feces was <1% of the administered dose. The American Society for Pharmacology and Experimental Therapeutics