Table 2.
Summary of the pharmacokinetics based on the dose level and treatment day from the 2 Z-endoxifen phase 1 clinical trials
| Dose level (mg) | No. of patients | Day | Tmax (h) | Cmax (ng/mL) | C24h (ng/mL) | AUC0-24h (hours × µg/mL) | Accumulation (AUC) | Half-life (h) |
|---|---|---|---|---|---|---|---|---|
| Goetz et al study, 2017 (49) | ||||||||
| 20 | 3 | 1 | 4.3 ± 3.2 | 64.8 ± 13.2 | 38.1 ± 3.7 | 1.09 ± 0.21 | 3.47 ± 1.29 | 49.0 ± 21.7 |
| 2 | 28 | 3.5 ± 3.5 | 215 ± 83 | 167 ± 49 | 4.19 ± 1.46 | |||
| 40 | 8 | 1 | 3.6 ± 2.3 | 169 ± 49 | 86.6 ± 22.6 | 2.49 ± 0.58 | 3.96 ± 0.89 | 57.2 ± 14.8 |
| 8 | 28 | 1.7 ± 1.0 | 499 ± 49 | 414 ± 111a | 9.66 ± 2.32 | |||
| 60 | 8 | 1 | 2.6 ± 0.9 | 348 ± 222 | 132 ± 93 | 4.33 ± 2.69 | 3.94 ± 1.86 | 56.5 ± 31.4 |
| 5 | 28 | 2.8 ± 0.8 | 643 ± 332 | 421 ± 216 | 11.6 ± 5.5 | |||
| 80 | 8 | 1 | 6.8 ± 7.3 | 238 ± 49 | 152 ± 39 | 4.15 ± 0.91 | 4.14 ± 1.28 | 60.2 ± 21.4 |
| 7 | 28 | 2.6 ± 1.7 | 913 ± 142 | 577 ± 122b | 15.8 ± 2.3 | |||
| 100 | 8 | 1 | 4.0 ± 2.8 | 344 ± 104 | 194 ± 43 | 5.62 ± 1.18 | 4.62 ± 1.10 | 68.1 ± 18.4 |
| 7 | 28 | 4.2 ± 3.1 | 1284 ± 364 | 952 ± 246 | 25.7 ± 6.8 | |||
| 120 | 3 | 1 | 3.0 ± 1.0 | 378 ± 155 | 243 ± 89 | 6.03 ± 2.73 | 3.64 ± 1.18 | 51.7 ± 19.7 |
| 3 | 28 | 2.7 ± 1.1 | 1261 ± 453 | 813 ± 235 | 20.7 ± 6.3 | |||
| 160 | 3 | 1 | 3.7 ± 2.1 | 635 ± 39 | 333 ± 62 | 9.81 ± 6.3 | 3.81 ± 0.76 | 54.6 ± 12.8 |
| 3 | 28 | 5.1 ± 4.0 | 1874 ± 633 | 1362 ± 379 | 37.9 ± 12.3 | |||
| Takebe et al study, 2021 (50) | ||||||||
| 20 | 3 | 1 | 3.7 ± 0.6 | 68.6 ± 7.9 | 30.2 ± 4.3 | 1.08 ± 0.07 | 3.9 ± 0.9 | 55.9 ± 15.0 |
| 3 | 28 | 0.7 ± 0.6 | 286.1 ± 86.8 | 131.7 ± 79.2 | 4.25 ± 1.19 | |||
| 40 | 5 | 1 | 4.0 ± 0.0 | 112.2 ± 30.2 | 52.5 ± 15.4 | 1.65 ± 0.36 | 3.0 ± 0.3 | 40.4 ± 4.4 |
| 3 | 28 | 3.3 ± 2.5 | 257.9 ± 55.0 | 147.3 ± 42.6 | 4.76 ± 0.85 | |||
| 60 | 3 | 1 | 12.0 ± 10.4 | 121.6 ± 39.7 | 82.7 ± 9.3 | 2.14 ± 0.63 | 3.7 ± 1.5 | 52.4 ± 25.2 |
| 3 | 28 | 10.8 ± 12.0 | 417.3 ± 188.6 | 345.4 ± 175.9 | 8.08 ± 4.05 | |||
| 100 | 3 | 1 | 4.3 ± 2.9 | 296.0 ± 30.0 | 155 ± 21 | 5.00 ± 0.46 | 2.7 ± N/A | 36.8 ± N/A |
| 3 | 28 | 3.0 ± 1.4 | 1010.0 ± 411.5 | 428.0 ± N/A | 13.29 ± N/A | |||
| 140 | 3 | 1 | 4.3 ± 1.5 | 610.0 ± 306.0 | 311.0 ± 171.0 | 9.76 ± 4.24 | 2.4 ± 0.2 | 30.6 ± 3.5 |
| 3 | 28 | 2.0 ± 1.0 | 1113.0 ± 325.0 | 563.0 ± 49.0 | 17.40 ± 1.15 | |||
| 200 | 3 | 1 | 4.0 ± 3.5 | 517.0 ± 232.0 | 336.0 ± 105.0 | 9.22 ± 3.11 | 3.1 ± 0.9 | 43.4 ± 15.8 |
| 3 | 28 | 2.0 ± 0.0 | 1641.0 ± 830.0 | 1069.0 ± 652.0 | 30.75 ± 19.43 | |||
| 280 | 7 | 1 | 3.0 ± 0.8 | 930.0 ± 224.0 | 468.0 ± 128.0 | 14.96 ± 4.64 | N/Ac | N/Ac |
| 360 | 7 | 1 | 3.9 ± 1.6 | 1309.0 ± 349.0 | 676.0 ± 297.0 | 20.55 ± 7.33 | N/Ac | N/Ac |
Data presented as mean ± SD.
Abbreviations: AUC, area under the curve; AUC0-24h, area under the curve over 24 h; C24h, serum concentration after 24 h; Cmax, peak serum concentration; N/A, not available; Tmax, time to maximum serum concentration.
a n = 7 as reported in Goetz et al study.
b n = 5 as reported in Goetz et al study.
c Pharmacokinetics on day 28 not reported for these doses in the Takebe et al study.