Abstract

We determined the disposition of a single 300-mg dose of [¹⁴C]celecoxib in eight healthy male subjects. The [¹⁴C]celecoxib was administered as a fine suspension reconstituted in 80 ml of an apple juice/Tween 80/ethanol mixture. Blood and saliva samples were collected at selected time intervals after dosing. All urine and feces were collected on the 10 consecutive days after dose administration. Radioactivity in each sample was determined by liquid scintillation counting or complete oxidation and liquid scintillation counting. Metabolic profiles in plasma, urine, and feces were obtained by HPLC, and metabolites were identified by mass spectrometry and NMR. [¹⁴C]Celecoxib was well absorbed, reaching peak plasma concentrations within 2 h of dosing. [¹⁴C]Celecoxib was extensively metabolized, with only 2.56% of the radioactive dose excreted as celecoxib in either urine or feces. The total percentage of administered radioactive dose recovered was 84.8 ± 4.9%, with 27.1 ± 2.2% in the urine and 57.6 ± 7.3% in the feces. The oxidative metabolism of celecoxib involved hydroxylation of celecoxib at the methyl moiety followed by further oxidation of the hydroxyl group to form a carboxylic acid metabolite. The carboxylic acid metabolite of celecoxib was conjugated with glucuronide to form the 1-O-glucuronide. The percentages of the dose excreted in the feces as celecoxib and the carboxylic acid metabolite were 2.56 ± 1.09 and 54.4 ± 6.8%, respectively. The majority of the dose excreted in the urine was the carboxylic acid metabolite (18.8 ± 2.1%); only a small amount was excreted as the acyl glucuronide (1.48 ± 0.15%).