Table 4.
In vitro evaluation of canagliflozin as an inhibitor of human CYP and UGT enzymes
| Enzyme | Enzyme reaction | Direct inhibition | |
|---|---|---|---|
| IC50 (SE) μmol l–1 | (%) Inhibition at 100 μmol l–1 | ||
| CYP1A2 | Phenacetin O‐deethylase | >100 | 25 |
| CYP2A6 | Coumarin 7‐hydroxylation | >100 | 41 |
| CYP2B6 | Bupropion 1‐hydroxylation | 16 (2.1) | 100 |
| CYP2C8 | Desethylation of amodiaquine | 75 (6.4) | 61 |
| CYP2C9 | Tolbutamide hydroxylation | 80 (8.1) | 56 |
| CYP2C19 | S‐Mephenytoin 4‐hydroxylation | >100 | 41 |
| CYP2D6 | Bufuralol 1′‐hydroxylation | >100 | 35 |
| CYP2E1 | 6‐Hydroxylation of chlorzoxazone | >100 | 4 |
| CYP3A4 | 6β‐Hydroxylation of testosterone | 27 (4.9) | 84 |
| CYP3A4/5 | Midazolam 1′‐hydroxylation | >100 | 21 |
| UGT1A1 | 17β‐Estradiol 3‐β‐D‐glucuronidation | 91 (53) | 45 |
| UGT1A4 | Trifluoperazine glucuronidation | >100 | 42 |
| UGT1A6 | 1‐Naphthol glucuronidation | 50 (4.0) | 78 |
| UGT1A9 | Propofol glucuronidation | > 100 | 40 |
| UGT2B7 | Morphine 3‐β‐D‐glucuronidation | > 100 | NA |
NA = Not applicable. Inhibition was not observed at the highest concentration tested.
IC50 = half maximal inhibitory concentration; SE = standard error. SE values presented for the IC50 estimates