Table 2.
Summary of pharmacokinetic parameters (geometric mean with percentage of coefficient of variation), except for Tmax median (range) following repeated oral dosing of AZD5718 in healthy Japanese subjects, n = 6 per dose level
| Dose, dosing regimen, day | Cmax (nmol/L) | Tmax (h) | AUCτ (nmol∙h/L) | CL/F (L/h) | t½ (h) | CLR (L/h) | TCP |
|---|---|---|---|---|---|---|---|
| 60 mg, OD, Day 1 | 140.5 (55.1) | 1.0 (1.0, 3.0) | 862.9 (35.8) | 142.1 (33.5) | 10.1 (44.0) | NE | NE |
| 60 mg, OD, Day 10 | 158.9 (25.1) | 2.0 (1.0, 3.0) | 1140.5 (25.5) | 117.8 (25.5) | 12.8 (47.0) | 0.8 (22.5) | 1.2 (14.9) |
| 180 mg, OD, Day 1 | 1277.0 (24.6) | 1.0 (0.5, 2.0) | 4739.4 (33.3) | 82.2 (35.8) | 8.5 (47.9) | NE | NE |
| 180 mg, OD, Day 10 | 1567.9 (28.6) | 1.5 (1.0, 2.0) | 6724.5 (32.0) | 60.0 (32.0) | 8.6 (23.6) | 0.8 (38.4) | 1.4 (14.1) |
| 360 mg, OD, Day 1 | 2196.3 (48.6) | 1.0 (1.0, 2.1) | 8971.1 (47.6) | 84.3 (51.7) | 15.0 (100.5) | NE | NE |
| 360 mg, OD, Day 10 | 3461.5 (40.4) | 2.0 (1.0, 3.0) | 15,847.3 (47.8) | 50.9 (47.8) | 10.5 (29.1) | 0.9 (21.0) | 1.7 (31.9) |
| 600 mg, OD, Day 1 | 5180.6 (24.2) | 1.0 (1.0, 2.0) | 17,592.6 (39.9) | 74.1 (40.0) | 7.4 (25.5) | NE | NE |
| 600 mg, OD, Day 10 | 6145.6 (40.0) | 1.0 (1.0, 2.0) | 27,349.3 (48.8) | 49.1 (48.8) | 8.5 (35.1) | 0.8 (16.8) | 1.5 (28.9) |
AUCτ area under the concentration–time curve over the dosing interval, CL/F oral plasma clearance, CLR renal clearance, Cmax peak plasma concentration, NE not estimated, OD once daily, t1/2 terminal half-life, Tmax time to peak concentration, TCP temporal change parameter in systemic exposure calculated as AUCτ Day 10/AUC Day 1