Chemical inhibition and formation of 3-hydroxydesloratadine in CHHs and recombinant enzymes
| Enzyme | Inhibitor | Inhibition of 3-OH Formation | Recombinant Enzyme Activity | ||
|---|---|---|---|---|---|
| 3-OH | 5-OHa | 6-OHa | |||
| % | |||||
| CYP | 1-ABT | 98 | NA | ||
| CYP1A1 | NA | NA | None | Yes | Yes |
| CYP1A2 | Furafylline | 0 | Noneb | Nonec | |
| CYP1B1 | NA | NA | |||
| CYP2A6 | |||||
| CYP2B6 | Phencyclidine | 13.3 | |||
| CYP2C8 | Gemfibrozil glucuronide | 91.3–100 | |||
| Gemfibrozil | 100 | ||||
| Montelukast | 100 | ||||
| Clopidogrel glucuronide | 78.9 | ||||
| Repaglinide | 73.3 | ||||
| Cerivastatin | 84.6 | ||||
| CYP2C9 | Tienilic acid | 0 | |||
| CYP2C18 | NA | NA | |||
| CYP2C19 | Esomeprazole | 22.5 | |||
| CYP2D6 | Paroxetine, Quinidine | 0 | Yes | Yes | |
| CYP2E1 | NA | NA | Noneb | Nonec | |
| CYP2J2 | |||||
| CYP3A4/CYP3A5 | Mibefradil | 0 | Yes (CYP3A4) | Yes (CYP3A4) | |
| CYP3cide | 0 | ||||
| Troleandomycin | 0 | ||||
| Ketoconazole | 27.0 | ||||
| CYP3A7 | NA | NA | Noneb | Nonec | |
| CYP4A11 | |||||
| CYP4F2 | |||||
| CYP4F3a | |||||
| CYP4F3b | |||||
| CYP4F12 | |||||
| FMO1 | |||||
| FMO3 | |||||
| FMO5 | |||||
3-OH, 3-hydroxydesloratadine; 5-OH, 5-hydroxydesloratadine; 6-OH, 6-hydroxydesloratadine; NA, not applicable.
↵a Data from 10-μM desloratadine experiments.
↵b Trace levels detected for CYP1A2, CYP1B1, CYP2B6, CYP2C8, CYP2C18, CYP2C19, CYP2J2, CYP3A5, and CYP3A7 with 1 μM desloratadine.
↵c Trace levels detected for CYP1A2, CYP1B1, CYP2B6, CYP2C8, CYP2C18, CYP2J2, and CYP3A7 with 1 μM desloratadine.