Table 3.
Pharmacokinetics parameters of abexinostat prototype, two main metabolites RTP-CC-190623-1 and RTP-CC-190623-2
| AUC0-t (h·ng/mL), Mean ± SD | AUC0-∞ (ng·h/mL), Mean ± SD | Cmax (ng/mL), Mean ± SD | Tmax (h), Median | T1/2 (h), Median | MRTlast (h), Median | |
|---|---|---|---|---|---|---|
| Abexinostat single dose administration on D-3 | ||||||
| Abexinostat prototype | ||||||
| 40 mg (n = 4) | 159 ± 12.1 | 171 ± 12.7 | 94.9 ± 11.4 | 0.500 | 2.56 | 2.80 |
| 60 mg (n = 3) | 225 ± 47.2 | 242 ± 41.0 | 89.8 ± 22.3 | 1.00 | 8.31 | 6.97 |
| 80 mg (n = 4) | 294 ± 76.5 | 309 ± 76.3 | 164 ± 60.7 | 0.990 | 4.81 | 3.47 |
| RTP-CC-190623-1 | ||||||
| 40 mg (n = 4) | 286 ± 119 | 268 ± 104 | 38.0 ± 12.4 | 1.00 | 7.75 | 9.92 |
| 60 mg (n = 3) | 422 ± 108 | 426 ± NC | 53.1 ± 10.7 | 1.00 | 9.82 | 11.6 |
| 80 mg (n = 4) | 533 ± 163 | 462 ± NC | 78.6 ± 10.8 | 1.49 | 5.86 | 6.74 |
| RTP-CC-190123-2 | ||||||
| 40 mg (n = 4) | 421 ± 175 | 33.1 ± 12.5 | 6.97 | |||
| 60 mg (n = 3) | 352 ± 83.4 | 26.0 ± 7.35 | 2.00 | |||
| 80 mg (n = 4) | 360 ± 92.1 | 373 ± NC | 34.6 ± 15.4 | 1.00 | 7.03 | 8.68 |
| Abexinostat continuous administration on C1D1 | ||||||
| 40 mg (n = 4) | 339 ± 90.9 | 361 ± 88.3 | 98.1 ± 27.6 | 1.00 | 3.69 | |
| 60 mg (n = 3) | 521 ± 60.6 | 563 ± 69.6 | 115 ± 24.2 | 4.55# | 6.28 | |
| 80 mg (n = 4) | 603 ± 104 | 625 ± 116 | 128 ± 25.3 | 4.78& | 5.13 | |
| RTP-CC-190623-1 | ||||||
| 40 mg (n = 4) | 523 ± 292 | 560 ± NC | 44.5 ± 18.0 | 5.59 | 7.07 | |
| 60 mg (n = 3) | 803 ± 186 | 902 ± NC | 68.3 ± 9.23 | 5.05 | 9.41 | |
| 80 mg (n = 4) | 1090 ± 229 | 1390 ± NC | 80.3 ± 10.5 | 6.02 | 7.68 | |
| RTP-CC-190123-2 | ||||||
| 40 mg (n = 4) | 586 ± 344 | 44.7 ± 19.3 | 10.0 | |||
| 60 mg (n = 3) | 718 ± 168 | 46.1 ± 13.3 | 23.9 | |||
| 80 mg (n = 4) | 766 ± 144 | 44.7 ± 17.7 | 6.03 | |||
| Abexinostat continuous administration on C1D7 | ||||||
| 40 mg (n = 4) | 463 ± 32.5 | 491 ± 43.7 | 107 ± 16.3 | 1.00 | 4.84 | |
| 60 mg (n = 3) | 600 ± 53.8 | 656 ± 72.0 | 104 ± 26.9 | 0.480 | 6.53 | |
| 80 mg (n = 4) | 767 ± 140 | 744 ± 132 | 184 ± 27.0 | 2.74 | 5.03 | |
| RTP-CC-190623-1 | ||||||
| 40 mg (n = 4) | 837 ± 263 | 50.6 ± 5.45 | 1.97 | |||
| 60 mg (n = 3) | 1870 ± 874 | 113 ± 41.7 | 0.980 | |||
| 80 mg (n = 4) | 1910 ± 604 | 151 ± 29.6 | 2.99 | |||
| RTP-CC-190123-2 | ||||||
| 40 mg (n = 4) | 1010 ± 287 | 62.6 ± 21.5 | 9.92 | |||
| 60 mg (n = 3) | 1820 ± 668 | 98.3 ± 42.7 | 23.9 | |||
| 80 mg (n = 4) | 1650 ± 503 | 105 ± 21.0 | 6.02 | |||
Missing data indicates that there were no patient pharmacokinetics parameters available to calculate the corresponding data
AUC0-t Area under the concentration–time curve from time zero to time t, AUC0-∞ area under the concentration–time curve from time zero to infinite time, Cmax maximum concentration, Tmax time to peak drug concentration, T1/2 elimilation half-life, MRTlast residence time from the time of dosing to the time of the last measurable concentration, SD standard deviation
# 0.5 h after second dose of abexinostat; & 0.97 h after second dose of abexinostat