Table 3.
Predicted steady-state brensocatib PPK parameters
| Parameter, mean (CV%) |
Phase I | Phase II | |||
|---|---|---|---|---|---|
| 10 mg (n = 16) | 25 mg (n = 17) | 40 mg (n = 35) | 10 mg (n = 75) | 25 mg (n = 82) | |
| AUCτ, ng·h/mL | 1110 (27.1) | 3660 (35.3) | 5420 (37.1) | 1760 (34.0) | 4540 (42.3) |
| Cmax, ng/mL | 76.2 (21.1) | 257 (33.0) | 401 (35.7) | 101 (30.3) | 260 (37.0) |
| Tmax, h | 1.13 (32.9) | 1.26 (22.8) | 1.27 (37.5) | 1.27 (6.55) | 1.27 (7.20) |
| Cmin, ng/mL | 27.7 (40.5) | 93.1 (43.3) | 131 (49.1) | 54.4 (40.7) | 140 (51.0) |
| CL/F, L/h | 9.05 (27.1) | 6.83 (35.3) | 7.38 (37.1) | 5.68 (34.0) | 5.51 (42.4) |
| Vc/F, L | 197 (24.1) | 141 (34.5) | 139 (43.4) | 207 (31.2) | 203 (34.8) |
| t½,α, h | 5.20 (15.3) | 4.58 (18.1) | 4.54 (24.7) | 5.83 (22.3) | 5.74 (22.1) |
| t½,β, h | 24.3 (23.6) | 26.0 (20.3) | 25.3 (26.5) | 38.5 (26.7) | 39.1 (34.2) |
AUCτ area under the plasma concentration–time curve from time 0 to 24 h, Cmax maximum plasma concentration, Cmin minimum plasma concentration, CL/F apparent oral clearance, CV coefficient of variation, PPK population pharmacokinetics, t½,α half-life of the first distributional phase, t½,β half-life of the second distributional phase, Tmax time at maximum concentration, Vc/F apparent oral volume of distribution of the central compartment