TABLE 2.
Unadjusted pharmacokinetic parameters (mean ± SD)
| TX-004HR | Placebo (n = 17) | |||
| 4 μg (n = 18) | 10 μg (n = 19) | 25 μg (n = 18) | ||
| Estradiol | ||||
| Day 1 | ||||
| AUC, pg×h/mL | 91.7 ± 37.9 | 138.2 ± 75.2 | 217.4 ± 99.0a | 116.6 ± 77.3 |
| Cmax, pg/mL | 6.5 ± 2.1 | 10.9 ± 5.0b | 29.8 ± 17.5c | 6.6 ± 4.9 |
| Cavg, pg/mL | 3.9 ± 1.5 | 5.8 ± 3.1 | 9.1 ± 4.1a | 4.9 ± 3.2 |
| Cmin, pg/mL | 3.3 ± 1.3 | 4.4 ± 2.7 | 3.5 ± 1.7 | 3.9 ± 2.6 |
| tmax, h | 7.0 ± 9.4 | 6.1 ± 8.0 | 4.6 ± 7.1 | 8.6 ± 6.7 |
| Day 14 | ||||
| AUC, pg×h/mL | 87.2 ± 42.8 | 110.1 ± 54.6 | 171.6 ± 80.1b | 104.2 ± 66.4 |
| Cmax, pg/mL | 4.8 ± 2.3 | 7.3 ± 2.4 | 15.7 ± 7.6c | 5.5 ± 3.4 |
| Cavg, pg/mL | 3.6 ± 1.8 | 4.6 ± 2.3 | 7.1 ± 3.3b | 4.3 ± 2.8 |
| Cmin, pg/mL | 3.2 ± 1.5 | 3.6 ± 1.9 | 4.3 ± 2.5 | 3. 4 ± 2.1 |
| tmax, h | 9.3 ± 8.9 | 4.0 ± 2.6a | 2.7 ± 1.9c | 7.2 ± 3.0 |
| Estrone | ||||
| Day 1 | ||||
| AUC, pg×h/mL | 290.2 ± 123.7b | 462.7 ± 195.6 | 419.1 ± 147.9 | 467.9 ± 278.8 |
| Cmax, pg/mL | 15.8 ± 6.1b | 23.5 ± 9.9 | 21.9 ± 7.7 | 25.7 ± 18.4 |
| Cavg, pg/mL | 13.0 ± 4.7b | 19.3 ± 8.2 | 17.5 ± 6.2 | 19.5 ± 11.6 |
| Cmin, pg/mL | 11.6 ± 4.3 | 17.1 ± 7.5 | 15.0 ± 5.8 | 16.5 ± 10.0 |
| tmax, h | 14.1 ± 9.4 | 11.9 ± 9.8 | 9.1 ± 7.4 | 12.1 ± 9.4 |
| Day 14 | ||||
| AUC, pg×h/mL | 326.6 ± 114.1 | 464.1 ± 243.9 | 428.7 ± 161.7 | 426.8 ± 180.7 |
| Cmax, pg/mL | 16.0 ± 5.5b | 23.9 ± 13.5 | 22.4 ± 8.9 | 22.8 ± 10.9 |
| Cavg, pg/mL | 13.6 ± 4.8 | 19.3 ± 10.2 | 17.9 ± 6.7 | 17.8 ± 7.5 |
| Cmin, pg/mL | 12.2 ± 4.4 | 17.4 ± 8.5 | 16.0 ± 6.1 | 14.3 ± 7.1 |
| tmax, h | 10.9 ± 9.0 | 10.4 ± 8.9 | 6.3 ± 6.9b | 12.2 ± 9.2 |
| Estrone conjugates | ||||
| Day 1 | ||||
| AUC, pg×h/mL | 5078 ± 3798 | 5932 ± 4210 | 9126 ± 9186 | 5638 ± 3151 |
| Cmax, pg/mL | 273.1 ± 196.4 | 329.4 ± 226.6 | 542.1 ± 475.5 | 309.8 ± 146.1 |
| Cavg, pg/mL | 215.9 ± 154.8 | 247.2 ± 175.4 | 380.3 ± 382.8 | 244.6 ± 128.1 |
| Cmin, pg/mL | 178.3 ± 128.7 | 208.7 ± 137.0 | 288.0 ± 311.3 | 207.6 ± 146.0 |
| tmax, h | 10.9 ± 8.7 | 9.2 ± 9.3 | 5.4 ± 2.6a | 13.1 ± 9.7 |
| Day 14 | ||||
| AUC, pg×h/mL | 5173 ± 3383 | 8978 ± 9811 | 9930 ± 11710 | 6275 ± 3398 |
| Cmax, pg/mL | 289.0 ± 183.8 | 511.7 ± 568.8 | 579.5 ± 610.1 | 343.6 ± 182.2 |
| Cavg, pg/mL | 215.5 ± 141.0 | 374.1 ± 408.8 | 413.8 ± 488.0 | 261.5 ± 141.6 |
| Cmin, pg/mL | 174.3 ± 121.8 | 271.6 ± 285.0 | 303.7 ± 380.6 | 207. 8 ± 111.5 |
| t, h | 8.4 ± 7.8 | 9.0 ± 8.6 | 5.9 ± 2.9 | 8.1 ± 6.8 |
Data are unadjusted for baseline and represented as mean ± SD.
AUC, area under the serum concentration-time curve.
aP < 0.01, bP < 0.05, cP < 0.0001 versus placebo using t tests.