Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants
| Autor: | Hao Ming-Hong, Y. Amy Siu, W. George Lai, Vaishali Dixit |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Quinidine Models Molecular CYP2D6 Pharmaceutical Science Pharmacology digestive system Substrate Specificity Hydroxylation 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship medicine Humans heterocyclic compounds Pharmacology (medical) Enzyme Inhibitors skin and connective tissue diseases CYP2C9 Cytochrome P-450 CYP2C9 CYP3A4 Dose-Response Relationship Drug Molecular Structure organic chemicals Genetic Variation Dextromethorphan Recombinant Proteins Kinetics 030104 developmental biology chemistry Cytochrome P-450 CYP2D6 Celecoxib Microsome medicine.drug |
| Zdroj: | Drug metabolism and pharmacokinetics. 33(5) |
| ISSN: | 1880-0920 |
| Popis: | Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in vitro. In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate inhibition kinetics with apparent Km, Ki, and Vmax of 67.2 μM, 12.6 μM, and 1.33 μM/min, respectively. In human liver microsomes (HLMs), a concentration-dependent inhibition of celecoxib hydroxylation by quinidine was observed after CYP2C9 and CYP3A4 were inhibited. 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 |
| Databáze: | OpenAIRE |
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