Table 4.
Plasma GSK2816126 pharmacokinetic parameters based on actual sampling times for cycle 1, day 1 and cycle 1, day 15
| PK Para | Day | 50 mg | 100 mg | 200 mg | 400 mg | 800 mg |
|---|---|---|---|---|---|---|
| AUC(0–∞) (h*μg/mL) | 1 | 1.33 (82), n = 2 | NA (NA), n = 0 | NA (NA), n = 0 | 13.2 (NA), n = 1 | 26.4 (12), n = 3 |
| 15 | 3.90 (NA), n = 1 | 7.00 (NA), n = 1 | NA (NA), n = 0 | 14.8 (NA), n = 1 | 33.3 (24), n = 2 | |
| AUC(0–t) (h*μg/mL) | 1 | 1.20 (62), n = 2 | 27.2 (NA), n = 1 | 27.7 (NA), n = 1 | 11.8 (NA), n = 1 | 24.2 (10), n = 3 |
| 15 | 3.20 (NA), n = 1 | 5.70 (NA), n = 1 | 7.10 (NA), n = 1 | 13.1 (NA), n = 1 | 25.8 (30), n = 3 | |
| Cmax (μg/mL) | 1 | 0.42 (52), n = 2 | 1.10 (NA), n = 1 | 1.40 (NA), n = 1 | 4.00 (NA), n = 1 | 7.31 (16), n = 3 |
| 15 | 0.50 (NA), n = 1 | 1.00 (NA), n = 1 | 1.50 (NA), n = 1 | 3.50 (NA), n = 1 | 7.46 (13), n = 3 | |
| tmax (hours) | 1 | 1.50 (1.0, 2.0), n = 2 | 1.00 (1.0, 1.0), n = 1 | 2.00 (2.0, 2.0), n = 1 | 1.90 (1.9, 1.9), n = 1 | 1.00 (0.5, 1.9), n = 3 |
| 15 | 2.7 (2.7, 2.7), n = 1 | 2.0 (2.0, 2.0), n = 1 | 1.0 (1.0, 1.0), n = 1 | 1.0 (1.0, 1.0), n = 1 | 2.0 (1.9, 2.0), n = 3 | |
| t1/2 (hours) | 1 | 7.62 (96), n = 2 | NA (NA), n = 0 | NA (NA), n = 0 | 49.1 (NA), n = 1 | 26.5 (31), n = 3 |
| 15 | 46.50 (NA), n = 1 | 36.80 (NA), n = 1 | NA (NA), n = 0 | 39.70 (NA) | 27.35 (9), n = 2 | |
| CL (L/h) | 1 | 37.39 (73), n = 2 | NA (NA), n = 0 | NA (NA), n = 0 | 35.30 (NA), n = 1 | 32.49 (9), n = 3 |
| 15 | 17.2 (NA), n = 1 | 17.5 (NA), n = 1 | NA (NA), n = 0 | 32.5 (NA), n = 1 | 26.8 (23), n = 2 | |
| V (L) | 1 | 194 (37), n = 2 | NA (NA), n = 0 | NA (NA), n = 0 | 722 (NA), n = 1 | 467 (15), n = 3 |
| 15 | 757 (NA), n = 1 | 598 (NA), n = 1 | NA (NA), n = 0 | 887 (NA), n = 1 | 601 (26), n = 2 | |
| PK Para | Visit Day | 1,200 mg | 1,800 mg | 2,400 mg | 3,000 mg | |
| AUC(0–∞) (h*μg/mL) | 1 | 60.9 (NA), n = 1 | 51.2 (23), n = 10 | 102 (28), n = 10 | 103 (48), n = 7 | |
| 15 | 60.2 (10), n = 1 | 81.7 (70), n = 9 | 123 (27), n = 11 | 183 (32), n = 4 | ||
| AUC(0–t) (h*μg/mL) | 1 | 85.7 (91), n = 4 | 45.9 (23), n = 10 | 92.4 (26), n = 12 | 94.0 (48), n = 7 | |
| 15 | 53.4 (14), n = 4 | 68.7 (75), n = 9 | 105 (29), n = 11 | 158 (35), n = 4 | ||
| Cmax (μg/mL) | 1 | 10.9 (10), n = 4 | 13.0 (27), n = 10 | 22.3 (35), n = 12 | 23.8 (21), n = 7 | |
| 15 | 11.6 (27), n = 4 | 14.2 (27), n = 9 | 21.6 (27), n = 11 | 30.5 (14), n = 4 | ||
| tmax (hours) | 1 | 2.05 (1.1, 72), n = 4 | 1.95 (1.0, 2.9), n = 10 | 2.00 (0.8, 2.8), n = 12 | 2.00 (0.5, 3.3), n = 7 | |
| 15 | 2.05 (2.0, 2.1), n = 4 | 1.90 (0.5, 2.7), n = 9 | 2.00 (1.0, 3.0), n = 11 | 2.25 (2.0, 3.0), n = 4 | ||
| t1/2 (hours) | 1 | 14.1 (NA), n = 1 | 31.8 (17), n = 10 | 33.7 (20), n = 10 | 22.5 (56), n = 7 | |
| 15 | 27.30 (18), n = 4 | 29.88 (50), n = 9 | 22.75 (44), n = 11 | 27.25 (44), n = 4 | ||
| CL (L/h) | 1 | 20.50 (NA), n = 1 | 39.01 (24), n = 10 | 26.06 (27), n = 10 | 28.60 (32), n = 7 | |
| 15 | 22.6 (14), n = 4 | 30.9 (25), n = 9 | 22.2 (25), n = 11 | 19.0 (36), n = 4 | ||
| V (L) | 1 | 284 (NA), n = 1 | 702 (50), n = 10 | 482 (31), n = 10 | 434 (74), n = 7 | |
| 15 | 499 (37), n = 4 | 918 (111), n = 9 | 424 (33), n = 11 | 480 (72), n = 4 |
Abbreviations: NA, not applicable; Par, parameter; PK, pharmacokinetic; t1/2, apparent terminal phase half-life; tmax, time to Cmax; V, volume.
a
Values denote geometric mean (CVb%) except for tmax, which is presented as median (range).