Pub. Date : 2018 Oct
PMID : 30219715
9 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants. | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 2 | Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants. | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 3 | Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in vitro. | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 4 | In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate inhibition kinetics with apparent Km, Ki, and Vmax of 67.2 muM, 12.6 muM, and 1.33 muM/min, respectively. | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 5 | In individual HLMs with variable CYP2D6 activities, a significant correlation was observed between celecoxib hydroxylation and CYP2D6-selective dextromethorphan O-demethylation when CYP2C9 and CYP3A4 activities were suppressed (r = 0.97, P < 0.0001). | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 6 | In individual HLMs with variable CYP2D6 activities, a significant correlation was observed between celecoxib hydroxylation and CYP2D6-selective dextromethorphan O-demethylation when CYP2C9 and CYP3A4 activities were suppressed (r = 0.97, P < 0.0001). | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 7 | Molecular modeling showed two predominant docking modes of celecoxib with CYP2D6, resulting in either a substrate or an inhibitor. | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 8 | Using HLMs from individual donors, the relative contribution of CYP2D6 to celecoxib metabolism was found to be highly variable and dependent on CYP2C9 genotypes, ranging from no contribution in extensive metabolizers with CYP2C9*1*1 genotype to approximately 30% in slow metabolizers with allelic variants CYP2C9*1*3 and CYP2C9*3*3. | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 9 | These results demonstrate that celecoxib may become a potential victim of CYP2D6-associated drug-drug interactions, particularly in individuals with reduced CYP2C9 activity. | Celecoxib | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |