Table 2. Inhibitory Potency and Inactivation Kinetic Parameters of NVP and 12-d3-NVP for Midazolam 1′-Hydroxylation by the Recombinant CYP3A4 Enzymea.
| NVP | 12-d3-NVP | |
|---|---|---|
| IC50 shift assay | IC50 ± SE (μM) (R2) | |
| 0 min preincubation | 23.9 ± 2.0 (0.983) | 11.3 ± 1.9 (0.943) |
| 30 min preincubation (−) NADPH | 30.0 ± 2.8 (0.974) | 9.38 ± 1.57 (0.948) |
| 30 min preincubation (+) NADPH | 5.30 ± 1.01 (0.935) | 2.85 ± 0.44 (0.976) |
| IC50 shift [(−)NADPH/(+)NADPH] | 5.7 | 3.3 |
| Inactivation assay | ||
| KI ± SE (μM) | 168 ± 22 | 112 ± 18 |
| kinact ± SE (min–1) | 0.148 ± 0.009 | 0.0977 ± 0.0061 |
| R2 | 0.991 | 0.982 |
| kinact/KI (mM–1·min–1) | 0.881 | 0.872 |
a
NVP, nevirapine; SE, standard error.