PBPK model–predicted pharmacokinetic parameters of crizotinib in healthy subjects following 28-day multiple oral administration of crizotinib with and without coadministration of ketoconazole or rifampin
Data are expressed as geometric mean with percent coefficient of variation (CV%) in parentheses (n = 15 per group × 6 groups). Dose levels were crizotinib 150 mg twice daily and ketoconazole 200 mg twice daily in the crizotinib-ketoconazole interaction and crizotinib 250 mg twice daily and rifampin 600 mg once daily in the crizotinib-rifampin interaction.
| Control Group | Treatment Group | Fold Increasea | |||||
|---|---|---|---|---|---|---|---|
| Interacting Drug | Cmax | AUC0–τ | Cmax | AUC0–τ | CmaxR | AUCR | |
| ng/ml | ng⋅h/ml | ng/ml | ng⋅h/ml | ratio | ratio | ||
| Ketoconazole | Predicted (on)b | 114 (57) | 1359 (57) | 250 (38) | 2978 (38) | 2.2 (47) | 2.2 (47) |
| Predicted (off)b | 66 (45) | 791 (46) | 221 (38) | 2619 (38) | 3.3 (33) | 3.3 (34) | |
| On/Offc | 1.7 | 1.7 | 1.1 | 1.1 | 0.66 | 0.67 | |
| Rifampin | Predicted (on)b | 225 (54) | 2694 (54) | 24 (118) | 275 (119) | 0.11 (68) | 0.10 (69) |
| Predicted (off)b | 110 (45) | 1319 (46) | 15 (65) | 176 (65) | 0.14 (48) | 0.13 (48) | |
| On/Offc | 2.0 | 2.0 | 1.6 | 1.6 | 0.77 | 0.76 | |