Table 3.
Summary of the pharmacokinetic parameters (geometric mean and percentage of coefficient of variation, except for Tmax median (range)) following single and repeated once daily dosing of AZD4831 in healthy volunteers
| Parameter | First day | Last day | |||||
|---|---|---|---|---|---|---|---|
| 5 mg (n = 8) | 10 mg (n = 8) | 15 mg (n = 8) | 45 mg (n = 5) a | 5 mg (n = 8) | 10 mg (n = 8) | 15 mg (n = 8) | |
| AUCτ, hour·nM | 206.1 (17.0) | 438.1 (19.5) | 660.8 (11.1) | 2,381 a (9.7) | 655.5 (19.6) | 1,450 (24.7) | 2,208 (18.7) |
| Cmax, nM | 16.5 (17.7) | 48.9 (24.7) | 66.2 (37.1) | 236.2 (52.7) | 37.3 (19.1) | 93.0 (21.0) | 145.7 (19.7) |
| t½ λz, hour | NE | NE | NE | NE | 53.3 (16.4) | 72.6 (14.6) | 71.8 (10.1) |
| CL/F, L/hour | NE | NE | NE | NE | 22.8 (19.6) | 20.6 (24.7) | 20.3 (18.7) |
| Tmax, hour | 1.0 (0.2‐2.0) | 1.0 (0.4‐1.5) | 1.0 (0.2‐1.5) | 0.6 (0.5‐3.0) | 1.8 (0.5‐4.0) | 1.0 (0.5‐4.0) | 1.0 (0.5‐3.0) |
| CLR, L/hour | 11.3 (27.7) | 11.8 (45.6) | 13.6 (20.2) | 13.4 (23.4) | 11.1 (19.2) | 10.5 (33.3) | 10.7 (12.5) |
AUC, area under the concentration‐time curve; CL/F, oral plasma clearance; CLR, renal clearance; Cmax, peak plasma concentration; NE, not estimated; t½λz, terminal half‐life; Tmax, time of maximum plasma concentration.
a
n = 4. One subject withdrew informed consent prior to 24 hours measurement.