Table 1.
Summary of primary and secondary pharmacokinetic parameters for probe substrates with and without a single 50-mg dose of osilodrostat (pharmacokinetic analysis set)
| Probe substrate | Treatment | AUClast (ng·h/mL) | AUCinf (ng·h/mL) | C max (ng/mL) | Half-life (h) | CL/F (L/h) |
|---|---|---|---|---|---|---|
| Caffeine (CYP1A2) | Substrate alone | 17,200 (61.7) | 16,200 (44.8) | 2500 (29.5) | 5.39 (58.1) | 6.18 (44.8) |
| Substrate plus osilodrostat | 41,100 (37.5) | 41,900 (32.1) | 2640 (20.1) | 7.39 (48.4) | 2.39 (32.1) | |
| Omeprazole (CYP2C19) | Substrate alone | 460 (97.0) | 618 (92.9) | 271 (69.7) | 0.77 (48.4) | 32.3 (92.9) |
| Substrate plus osilodrostat | 852 (90.7) | 885 (89.9) | 420 (70.8) | 0.87 (43.9) | 22.6 (89.9) | |
| Dextromethorphan (CYP2D6) | Substrate alone | 7.63 (1758.1) | 22.8 (193.8) | 1.24 (330.9) | 7.63 (87.5) | 1310 (193.8) |
| Substrate plus osilodrostat | 12.6 (1857.4) | 20.0 (233.9) | 1.80 (332.6) | 7.71 (107.4) | 1500 (233.9) | |
| Midazolam (CYP3A4/5) | Substrate alone | 21.2 (40.2) | 22.0 (39.6) | 8.78 (38.8) | 4.44 (38.3) | 91.0 (39.6) |
| Substrate plus osilodrostat | 31.7 (34.2) | 32.8 (34.1) | 12.8 (26.9) | 4.81 (35.1) | 61.0 (34.1) |
Data are shown as geometric mean (CV%)
AUC inf area under the concentration-time curve from time zero extrapolated to infinity, AUC last area under the concentration-time curve from time zero to the last measureable concentration, CL/F apparent total clearance, C max maximum plasma concentration, CV% coefficient of variation, CYP cytochrome P450