Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog, cynomolgus monkey and rhesus monkey

1. The metabolism and excretion of celecoxib, a specific cyclooxygenase 2 ( COX-2) inhibitor, was investigated in mouse, rabbit, the EM(extensive) and PM(poor metabolizer) dog, and rhesus and cynomolgus monkey. 2. Some sex and species differences were evident in the disposition of cele coxib. After intravenous (i.v.) administration of [C-14] celecoxib, the maj or route of excretion of radioactivity in all species studied was via the f aeces: EM dog (80.0%), PM dog (83.4%), cynomolgus monkey (63.5%), rhesus mo nkey (83.1%). After oral administration, faeces were the primary route of e xcretion in rabbit (72.2%) and the male mouse (71.1%), with the remainder o f the dose excreted in the urine. After oral administration of [C-14] celec oxib to the female mouse, radioactivity was eliminated equally in urine (45 .7%) and faeces (46.7%). 3. Biotransformation of celecoxib occurs primarily by oxidation of the arom atic methyl group to form a hydroxymethyl metabolite, which is further oxid ized to the carboxylic acid analogue. 4. An additional phase I metabolite (phenyl ring hydroxylation) and a glucu ronide conjugate of the carboxylic acid metabolite was produced by rabbit. 5. The major excretion product in urine and faeces of mouse, rabbit, dog an d monkey was the carboxylic acid metabolite of celecoxib.