Comparison of celecoxib metabolism and excretion in mouse, rabbit, dog, cynomolgus monkey and rhesus monkey
| Autor: | Y. M. Lawal, Susan K. Paulson, M. A. Berge, A. P. Breau, N. W. K. Liu, S. M. Jessen, Y. F. Wang, Josh J. Yuan, C. S. Markos, Jeremy D. Hribar, D. Yang, C. M. Dudkowski, J. W. A. Findlay, M. Chang, Ji Y. Zhang |
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| Rok vydání: | 2000 |
| Předmět: |
Male
medicine.medical_specialty Health Toxicology and Mutagenesis Metabolite Urine Biology Toxicology Biochemistry Mass Spectrometry Excretion chemistry.chemical_compound Feces Mice Dogs Pharmacokinetics Species Specificity Oral administration Internal medicine medicine Animals Cyclooxygenase Inhibitors Chromatography High Pressure Liquid Pharmacology Sulfonamides General Medicine Macaca mulatta Macaca fascicularis Endocrinology chemistry Celecoxib biology.protein Pyrazoles Female Cyclooxygenase Rabbits Glucuronide medicine.drug |
| Zdroj: | Xenobiotica; the fate of foreign compounds in biological systems. 30(7) |
| ISSN: | 0049-8254 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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