7
44
Disposition of ["%C]celecoxib in several species
After i.v. dosing to monkey and dog, excretion of the radioactivity was near
complete in rhesus monkey and EM and PM dog by 48 h after dose administration.
In the cynomolgus monkey, most of the dose was excreted by 5 days after dose
administration. Most of the radioactivity was excreted in the faeces, suggesting that
for dog and monkey the major route of elimination for celecoxib is metabolism
followed by excretion of the metabolites in bile. Radiolabeled celecoxib was
administered by oral gavage to mouse and rabbit. Excretion of radioactivity was near
complete by 48 h in these species. Higher urinary excretion occurred in female
(
45.7%) compared with male (22.4%) mouse.
In conclusion, celecoxib was eliminated primarily by a single metabolic pathway,
i.e. hydroxylation of the aromatic methyl group of celecoxib and further oxidation
of the hydroxylated metabolite to a carboxylic acid metabolite. The major route of
elimination of celecoxib was metabolism followed by excretion of the metabolites in
the faeces, with the remainder of the metabolites excreted by the kidney.
Acknowledgements
Radiolabeled compounds were synthesized by Scott Harring at the Radio-
chemistry Department at G. D. Searle.
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