TABLE 3.
Pharmacokinetics of milademetan
| Pharmacokinetic parameter | Day 1 of cycle 1 | Day 21 of cycle 1 | ||||
|---|---|---|---|---|---|---|
|
Cohort 1 (60 mg/d) (n = 3) |
Cohort 2 (90 mg/d) (n = 11) |
Cohort 3 (120 mg/d) (n = 4) |
Cohort 1 (60 mg/d) (n = 2) |
Cohort 2 (90 mg/d) (n = 9) |
Cohort 3 (120 mg/d) (n = 1) |
|
| Cmax (ng/mL) | 429 (253) | 692 (231) | 1140 (549) | 625 (161) | 995 (415) | 1230 (NC) |
| Ctrough (ng/mL) | ‐ | ‐ | ‐ | 192 (29.7) | 389 (234) | 552 (NC) |
| Tmax (h) | 3.00 (2.02, 6.07) | 3.00 (2.92, 6.05) | 3.01 (2.87, 6.03) | 2.48 (1.95, 3.00) | 3.02 (2.00, 6.07) | 2.95 (2.95, 2.95) |
| AUCtau (ng·h/mL) | 4250 (2340) | 8380 (2660) | 14 900 (6330) | 7390 (2450) | 14 100 (6760) | 17 300 (NC) |
| AUClast (ng·h/mL) | ‐ | ‐ | ‐ | 10 300 (3830) | 20 300 (10 300) | 25 600 (NC) |
| AUCinf (ng·h/mL) | 6320 (3720) | 13 400 (5160) | 25 500 (10 700) | ‐ | ‐ | ‐ |
| t1/2 (h) | 15.1 (2.74) | 15.4 (3.06) | 17.9 (4.09) | 18.1 (6.90) | 20.9 (3.25) | 26.1 (NC) |
| Accumulation rate | ‐ | ‐ | ‐ | 3.11 (2.57) | 1.65 (0.440) | 1.18 (NC) |
Abbreviations: AUC, area under the concentration‐time curve; AUCinf, AUC up to infinity; AUClast, AUC up to the last quantifiable time; AUCtau, AUC during dosing interval; Cmax, maximum plasma concentration; Ctrough, trough plasma concentration; NC, not calculated; ‐, not applicable. Values are means (standard deviations) for all parameters, except Tmax which is median (minimum, maximum).