Inhibition effects of apixaban on P450 enzyme activities in human liver microsomes
The concentrations of probe substrates used were at their Km values. The incubations were for 5 to 40 min at 0.05 to 0.25 mg/ml of proteins and 37°C.
| Enzyme | Probe Substrate Assay | IC50 for Apixaban | Positive Control | |
|---|---|---|---|---|
| Name | IC50 | |||
| μM | μM | |||
| CYP1A2 | Phenacetin O-deethylation | >45 | α-Naphthoflavone | 0.0068 |
| CYP2A6 | Coumarin 7-hydroxylation | >45 | Tranylcypromine | 0.077 |
| CYP2B6 | Bupropion hydroxylation | >45 | Orphenadrine | 464.7 |
| CYP2C8 | Paclitaxel 6α-hydroxylation | >45 | Montelukast | 0.0882 |
| CYP2C9 | Diclofenac 4′-hydroxylation | >45 | Sulfaphenazole | 0.528 |
| CYP2C19 | (S)-Mephenytoin 4′-hydroxylation | >20 | N-3-Benzylnirvanol | 0.399 |
| CYP2D6 | Dextromethorphan O-demethylation | >45 | Quinidine | 0.0526 |
| CYP3A4 | Midazolam 1′-hydroxylation | >45 | Ketoconazole | 0.0302 |
| CYP3A4 | Testosterone 6β-hydroxylation | >45 | Ketoconazole | 0.0451 |