RT Journal Article
SR Electronic
T1 Pharmacokinetics, Tissue Distribution, Metabolism, and Excretion of Celecoxib in Rats
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 514
OP 521
VO 28
IS 5
A1 Susan K. Paulson
A1 Ji Y. Zhang
A1 Alan P. Breau
A1 Jeremy D. Hribar
A1 Norman W. K. Liu
A1 Susan M. Jessen
A1 Yvette M. Lawal
A1 J. Nita Cogburn
A1 Christopher J. Gresk
A1 Charles S. Markos
A1 Timothy J. Maziasz
A1 Grant L. Schoenhard
A1 Earl G. Burton
YR 2000
UL http://dmd.aspetjournals.org/content/28/5/514.abstract
AB The pharmacokinetics, tissue distribution, metabolism, and excretion of celecoxib, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide, a cyclooxygenase-2 inhibitor, were investigated in rats. Celecoxib was metabolized extensively after i.v. administration of [14C]celecoxib, and elimination of unchanged compound was minor (less than 2%) in male and female rats. The only metabolism of celecoxib observed in rats was via a single oxidative pathway. The methyl group of celecoxib is first oxidized to a hydroxymethyl metabolite, followed by additional oxidation of the hydroxymethyl group to a carboxylic acid metabolite. Glucuronide conjugates of both the hydroxymethyl and carboxylic acid metabolites are formed. Total mean percent recovery of the radioactive dose was about 100% for both the male rat (9.6% in urine; 91.7% in feces) and the female rat (10.6% in urine; 91.3% in feces). After oral administration of [14C]celecoxib at doses of 20, 80, and 400 mg/kg, the majority of the radioactivity was excreted in the feces (88–94%) with the remainder of the dose excreted in the urine (7–10%). Both unchanged drug and the carboxylic acid metabolite of celecoxib were the major radioactive components excreted with the amount of celecoxib excreted in the feces increasing with dose. When administered orally, celecoxib was well distributed to the tissues examined with the highest concentrations of radioactivity found in the gastrointestinal tract. Maximal concentration of radioactivity was reached in most all tissues between 1 and 3 h postdose with the half-life paralleling that of plasma, with the exception of the gastrointestinal tract tissues. The American Society for Pharmacology and Experimental Therapeutics