TABLE 1.
Calculated fraction of the disposition pathway mediated by CYP3A (DPI3A) of victim drugs sorted by their CYP3A sensitivitiesb
| Drug | DPI3A |
Reference(s)a | Predicted AUC*/AUC with: |
||||
|---|---|---|---|---|---|---|---|
| Ritonavir (inhibitor) |
Etravirine (inducer) |
||||||
| Single calculation | Monte Carlo simulation | Single calculation | Monte Carlo simulation | Single calculation | Monte Carlo simulation | ||
| Simvastatin | 0.978 | 0.979 [0.916, 1.0] | 12 | 45.97 | 34.54 [5.33, 100.0] | 0.34 | 0.31 [0.12, 0.44] |
| Triazolam | 0.959 | 0.966 [0.898, 1.0] | 30, 31 | 24.39 | 24.97 [4.91, 100.0] | 0.35 | 0.31 [0.12, 0.44] |
| Midazolam | 0.940 | 0.940 [0.909, 0.971] | 32–35 | 16.67 | 12.36 [5.40, 20.64] | 0.35 | 0.32 [0.13, 0.45] |
| Quetiapine | 0.896 | 0.845 [0.645, 1.0] | 37 | 9.66 | 7.97 [2.42, 62.46] | 0.36 | 0.34 [0.14, 0.47] |
| Tacrolimus | 0.875 | 0.831 [0.531, 1.0] | 36 | 8.03 | 10.20 [1.97, 100.0] | 0.37 | 0.34 [0.14, 0.48] |
| Maraviroc | 0.828 | 0.792 [0.559, 0.998] | 38 | 5.80 | 5.85 [1.98, 31.26] | 0.38 | 0.35 [0.14, 0.49] |
| Saquinavir | 0.638 | 0.580 [0.258, 0.849] | 39 | 2.76 | 2.88 [1.31, 6.04] | 0.44 | 0.42 [0.18, 0.57] |
| Darunavir | 0.602 | 0.543 [0.215, 0.817] | 40 | 2.51 | 2.62 [1.26, 5.19] | 0.46 | 0.43 [0.18, 0.59] |
| Macitentan | 0.585 | 0.524 [0.200, 0.810] | 41 | 2.41 | 2.55 [1.24, 4.98] | 0.47 | 0.43 [0.19, 0.59] |
| Amlodipine | 0.468 | 0.464 [0.117, 1.0] | 16 | 1.88 | 2.75 [1.12, 30.13] | 0.52 | 0.46 [0.19, 0.64] |
| Etravirine | 0.340 | 0.336 [0.077, 0.701] | 42 | 1.52 | 1.79 [1.08, 3.18] | 0.60 | 0.52 [0.24, 0.71] |
| Rilpivirine | 0.324 | 0.334 [0.079, 0.656] | 43 | 1.48 | 1.73 [1.08, 2.84] | 0.61 | 0.53 [0.24, 0.71] |
| Zolpidem | 0.268 | 0.303 [0.065, 0.661] | 44, 45 | 1.37 | 1.66 [1.06, 2.79] | 0.66 | 0.55 [0.25, 0.73] |
| Ritonavir | 0.156 | 0.231 [0.038, 0.552] | 46 | 1.19 | 1.46 [1.04, 2.19] | 0.77 | 0.60 [0.29, 0.78] |
a
References reporting observed AUC ratios used to calculate DPI3A according to equation 3. If more than one study reported the AUC ratio for the same drug combination, the weighted mean was used to derive DPI3A.
b
Single calculations not considering variability and Monte Carlo simulations (n = 10,000) were performed to predict DDI magnitudes with the inhibitor ritonavir and the inducer etravirine. Results of the Monte Carlo simulations are presented as geometric means [95% confidence intervals].