The pharmacokinetics, tissue distribution, metabolism, and excretion of cel
ecoxib, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenes
ulfonamide, a cyclooxygenase-2 inhibitor, were investigated in rats. Celeco
xib was metabolized extensively after i.v. administration of [C-14]celecoxi
b, and elimination of unchanged compound was minor (less than 2%) in male a
nd 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 hydr
oxymethyl group to a carboxylic acid metabolite. Glucuronide conjugates of
both the hydroxymethyl and carboxylic acid metabolites are formed. Total me
an percent recovery of the radioactive dose was about 100% for both the mal
e rat (9.6% in urine; 91.7% in feces) and the female rat (10.6% in urine; 9
1.3% in feces). After oral administration of [C-14]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 excr
eted in the feces increasing with dose. When administered orally, celecoxib
was well distributed to the tissues examined with the highest concentratio
ns of radioactivity found in the gastrointestinal tract. Maximal concentrat
ion of radioactivity was reached in most all tissues between 1 and 3 h post
dose with the half-life paralleling that of plasma, with the exception of t
he gastrointestinal tract tissues.