Inhibition of CYP enzymes by DTG in HLMs
| Substrate | MDI | |||
|---|---|---|---|---|
| Control Preincubationa IC50 | NADPH Preincubationb IC50 | Fold Change in IC50 | ||
| μMc | ||||
| CYP1A2 | Phenacetin | >100 | >100 | NC |
| CYP 2A6 | Coumarin | >100 | >100 | NC |
| CYP 2B6 | Bupropion | >100d | >100 | NC |
| CYP 2C8 | Rosiglitazone | >100 | >100 | NC |
| CYP 2C9 | Diclofenac | >100d | >100 | NC |
| CYP 2C19 | S-Mephenytoin | >100d | >100 | NC |
| CYP 2D6 | Bufuralol | >100d | >100 | NC |
| CYP 3A4 | Atorvastatin | 54 | 33 | 1.6 |
| CYP 3A4 | Nifedipine | >100d | 65 | >1.5 |
NC, not calculated.
↵a Microsomes (0.1 mg/ml), buffer and DTG preincubated for 20 minutes with probe substrate prior to initiation of reaction with NADPH.
↵b Microsomes (0.1 mg/ml), buffer and DTG preincubated for 20 minutes with NADPH prior to initiation of reaction with probe substrate.
↵c Control preincubation IC50 = direct inhibition IC50.
↵d P450 inhibition was observed but the percentage of inhibition at the highest DTG concentration tested (100 μM) was weak (20–40%) and insufficient to calculate an IC50.