Table 3.
AMG 232 pharmacokinetic parameters
| Cycle 1, day 1 | Cycle 1, day 7 | |||||||
|---|---|---|---|---|---|---|---|---|
| tmax, h | Cmax, ng/mL | AUC24h, ng⋅h/mL | tmax, h | Cmax, ng/mL | AUC24h, ng⋅h/mL | CL/F, L/h | AUC24h AR | |
| AMG 232 60 mg | ||||||||
| n | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 |
| Mean | NC | 669 | 3310 | NC | 665 | 5440 | 12.4 | 1.79 |
| SD | NC | 226 | 884 | NC | 210 | 2080 | 5.04 | 0.984 |
| AMG 232 60 mg + trametinib 2 mg | ||||||||
| n | 10 | 10 | 9 | — | — | — | — | — |
| Mean | NC | 520 | 2850 | — | — | — | — | — |
| SD | NC | 211 | 1120 | — | — | — | — | — |
| AMG 232 90 mg | ||||||||
| n | 4 | 4 | 3 | 3 | 3 | 3 | 3 | 3 |
| Mean | NC | 1790 | 7140 | NC | 1350 | 12 500 | 7.27 | 1.77 |
| SD | NC | 702 | 1100 | NC | 109 | 1670 | 1.05 | 0.291 |
| AMG 232 180 mg | ||||||||
| n | 5 | 5 | 4 | 5 | 5 | 5 | 5 | 4 |
| Mean | NC | 962 | 6540 | NC | 1410 | 17 100 | 17.7 | 2.38 |
| SD | NC | 463 | 3790 | NC | 791 | 11 900 | 14.8 | 0.834 |
| AMG 232 240 mg | ||||||||
| n | 3 | 3 | 0 | 2 | 2 | 2 | 2 | 0 |
| Mean | NC | 1280 | NC | NC | 2110 | 20 100 | 13.4 | NC |
| SD | NC | 194 | NC | NC* | NC* | NC* | NC* | NC |
| AMG 232 360 mg | ||||||||
| n | 10 | 10 | 8 | 8 | 8 | 8 | 8 | 6 |
| Mean | NC | 5090 | 27 900 | NC | 3520 | 34 700 | 22.5 | 1.11 |
| SD | NC | 2320 | 16 500 | NC | 2470 | 31 700 | 20.4 | 0.728 |
AR, accumulation ratio (AUC24h cycle 1, day 1/AUC24h cycle 1, day 7); Cmin, minimum observed serum concentration; NC, not calculated; SD, standard deviation.
*
Standard deviation is not reported when n ≤ 2.