Geometric mean (%CV) ixazomib plasma pharmacokinetic parameters on days 1 and 11 of cycle 1
| Parameter . | Ixazomib dose, mg/m2 . | ||||||
|---|---|---|---|---|---|---|---|
| 0.24 . | 0.48 . | 0.8 . | 1.2 . | 1.68 . | 2 . | 2.23 . | |
| Day 1 | |||||||
| N | 3 | 2 | 2 | 2 | 3 | 31* | 3 |
| Tmax, hours† | 1 (0.567–2) | 0.5, 1.5 | 0.55, 1 | 0.5, 1.05 | 1 (1–2.02) | 0.65 (0.25–3.97) | 1 (0.717–1.08) |
| Cmax, ng/mL | 2.10 (19) | 8.38, 12 | 14.2, 30.2 | 11.9, 46.1 | 19.3 (48) | 49.0 (66) | 105 (57) |
| AUC0–72, hours × ng/mL | NC | NC | 80, 138 | 94.1, 224 | 246 (25) | 379 (40) | 383, 450 |
| DN Cmax, ng/mL/mg | 4.86 (9) | 10.5, 13.3 | 9.47, 20.1 | 4.96, 15.9 | 6.22 (53) | 13.1 (68) | 25.8 (78) |
| DN AUC0–72, hours × ng/mL/mg | NC | NC | 53.3, 92 | 39.2, 77.2 | 79.3 (30) | 102 (43) | 81.5, 100 |
| Day 11 | |||||||
| N | 3 | 3 | 2 | 2 | 3 | 28‡ | 2 |
| Tmax, hours† | 1.1 (1.05–4.07) | 1 (0.5–1.17) | 0.55, 2 | 0.5, 0.5 | 1 (0.567–1.05) | 1 (0.5–23.6) | 0.533, 1.13 |
| Cmax, ng/mL | 2.50 (53) | 7.78 (63) | 20.9, 42.4 | 46.5, 66.5 | 86.0 (71) | 60.5 (51) | 75.9, 135 |
| AUC0–72, hours × ng/mL | 55.0 (27) | 156 (65) | 428, 488 | 605 | 658, 959 | 1060 (68) | 1810, 2020 |
| DN Cmax, ng/mL/mg | 5.80 (56) | 9.35 (56) | 13.9, 28.3 | 19.4, 22.9 | 27.8 (68) | 16.4 (53) | 16.1, 30 |
| DN AUC0–72, hours × ng/mL/mg | 128 (37) | 188 (58) | 285, 325 | 252 | 206, 331 | 287 (63) | 385, 449 |
| t1/2, hours | NC | 135 | NC | 125, 128 | 128 (20) | 116 (25) | 86.7, 98.7 |
| Accumulation ratio | NC | NC | 3.11, 6.1 | 6.43 | 3.06, 3.49 | 3.09 (55) | 4.5, 4.72 |
| Parameter . | Ixazomib dose, mg/m2 . | ||||||
|---|---|---|---|---|---|---|---|
| 0.24 . | 0.48 . | 0.8 . | 1.2 . | 1.68 . | 2 . | 2.23 . | |
| Day 1 | |||||||
| N | 3 | 2 | 2 | 2 | 3 | 31* | 3 |
| Tmax, hours† | 1 (0.567–2) | 0.5, 1.5 | 0.55, 1 | 0.5, 1.05 | 1 (1–2.02) | 0.65 (0.25–3.97) | 1 (0.717–1.08) |
| Cmax, ng/mL | 2.10 (19) | 8.38, 12 | 14.2, 30.2 | 11.9, 46.1 | 19.3 (48) | 49.0 (66) | 105 (57) |
| AUC0–72, hours × ng/mL | NC | NC | 80, 138 | 94.1, 224 | 246 (25) | 379 (40) | 383, 450 |
| DN Cmax, ng/mL/mg | 4.86 (9) | 10.5, 13.3 | 9.47, 20.1 | 4.96, 15.9 | 6.22 (53) | 13.1 (68) | 25.8 (78) |
| DN AUC0–72, hours × ng/mL/mg | NC | NC | 53.3, 92 | 39.2, 77.2 | 79.3 (30) | 102 (43) | 81.5, 100 |
| Day 11 | |||||||
| N | 3 | 3 | 2 | 2 | 3 | 28‡ | 2 |
| Tmax, hours† | 1.1 (1.05–4.07) | 1 (0.5–1.17) | 0.55, 2 | 0.5, 0.5 | 1 (0.567–1.05) | 1 (0.5–23.6) | 0.533, 1.13 |
| Cmax, ng/mL | 2.50 (53) | 7.78 (63) | 20.9, 42.4 | 46.5, 66.5 | 86.0 (71) | 60.5 (51) | 75.9, 135 |
| AUC0–72, hours × ng/mL | 55.0 (27) | 156 (65) | 428, 488 | 605 | 658, 959 | 1060 (68) | 1810, 2020 |
| DN Cmax, ng/mL/mg | 5.80 (56) | 9.35 (56) | 13.9, 28.3 | 19.4, 22.9 | 27.8 (68) | 16.4 (53) | 16.1, 30 |
| DN AUC0–72, hours × ng/mL/mg | 128 (37) | 188 (58) | 285, 325 | 252 | 206, 331 | 287 (63) | 385, 449 |
| t1/2, hours | NC | 135 | NC | 125, 128 | 128 (20) | 116 (25) | 86.7, 98.7 |
| Accumulation ratio | NC | NC | 3.11, 6.1 | 6.43 | 3.06, 3.49 | 3.09 (55) | 4.5, 4.72 |
AUC0-72, area under the ixazomib plasma concentration vs time curve from time zero to 72 hours after dose; Cmax, maximum observed plasma concentration; DN, dose-normalized; NC, not calculated; t1/2, terminal half-life; Tmax, time of Cmax. Individual values are reported if N < 3.
N = 27 for AUC0-72 and DN AUC0-72.
Values are median and range.
N = 27 for AUC0-72 and DN AUC0-72, 24 for t1/2, and 22 for accumulation ratio.