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

Abstract

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 celecoxib. After intravenous (i.v.) administration of [14C]celecoxib, the major route of excretion of radioactivity in all species studied was via the faeces: EM dog (80.0%), PM dog (83.4%), cynomolgus monkey (63.5%), rhesus monkey (83.1%). After oral administration, faeces were the primary route of excretion in rabbit (72.2%) and the male mouse (71.1%), with the remainder of the dose excreted in the urine. After oral administration of [14C]celecoxib 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 aromatic methyl group to form a hydroxymethyl metabolite, which is further oxidized to the carboxylic acid analogue. 4. An additional phase I metabolite (phenyl ring hydroxylation) and a glucuronide conjugate of the carboxylic acid metabolite was produced by rabbit. 5. The major excretion product in urine and faeces of mouse, rabbit, dog and monkey was the carboxylic acid metabolite of celecoxib.

Enhancement of antinociception by coadministration of nonsteroidal anti-inflammatory drugs and soluble epoxide hydrolase inhibitors

“…given to four animals to obtain the corresponding doseresponse. The doses were chosen in the therapeutic range from preliminary pharmacokinetic data, eicosanoid profiles, and current literature (20)(21)(22)(23). For instance, celecoxib was administered at higher doses because it has a larger volume of distribution and is less efficacious when compared with rofecoxib.…”

In vivo and in vitro metabolism of lefucoxib in rats

“…Still, no glucuronide conjugate metabolites of lefucoxib were found. It was reported that the metabolic pathway for celecoxib, another selective inhibitor of COX-2, involved oxidation of the aromatic methyl group to form a hydroxy metabolite, which underwent additional oxidation to a carboxylic acid metabolite in rats [13]. Another study reported that carboxylic acid metabolite of celecoxib could be determined by HPLC-UV [14], which was tried and thought to be helpful in detecting carboxylic acid metabolites of lefucoxib if they existed.…”

Analytical Procedure for Determination of Cyclooxygenase-2 Inhibitors in Biological Fluids by High Performance Liquid Chromatography: A Review

“…COX-2 is induced at inflammation sites [31,32] but is also found constitutively in brain, spinal cord, kidney and some other tissues [33][34][35]. Clinical studies indicate that celecoxib is metabolised in the liver via the oxidative pathway to the corresponding alcohol and carboxylic acid and is removed by renal excretion as a glucuronide metabolite [36]. The chemical structures of celecoxib, hydroxycelecoxib, and carboxycelecoxib are shown in Fig.…”