Pharmacokinetic parameters of paroxetine and CTP-347 on days 1 and 14
| Cmax | Day 1 AUC0–last | Day 14 AUCss | Accumulation Indexa | ||
|---|---|---|---|---|---|
| Day 1 | Day 14 | ||||
| ng/ml | h⋅ng/ml | ||||
| Paroxetine: Multidose PK | |||||
| Paroxetine 10 mg daily | |||||
| Patient no. | |||||
| 1 | 0.5 | 4.3 | 4.3 | 57.5 | 13.4 |
| 2 | 0.5 | 6.9 | 7.1 | 122.3 | 17.2 |
| 3 | 3.2 | 17.0 | 40.2 | 296.5 | 7.4 |
| 4 | 3.2 | 15.6 | 39.1 | 262.2 | 6.7 |
| 5 | 1.3 | 14.0 | 15.2 | 261.8 | 17.2 |
| 6 | 0.3 | 1.1 | 2.6 | 14.8 | 5.7 |
| 7 | 1.6 | 25.3 | 22.9 | 494.1 | 21.6 |
| 8 | 0.4 | 1.0 | 3.0 | 12.2 | 4.1 |
| 9 | 1.6 | 14.1 | 20.4 | 234.5 | 11.5 |
| 10 | 4.0 | 35.9 | 60.0 | 649.3 | 10.8 |
| Mean | 1.6 | 13.5 | 21.5 | 240.5 | 11.2 |
| S.D. | 1.4 | 11.0 | 19.4 | 207.1 | 10.7 |
| Median | 1.4 | 14.0 | 17.8 | 248.1 | 13.9 |
| CTP-347: Escalating dose PK | |||||
| CTP-347 10 mg daily | |||||
| Patient no. | |||||
| 49 | 2.8 | 7.1 | 31.6 | 91.0 | 2.9 |
| 52 | 10.7 | 34.2 | 195.7 | 650.0 | 3.3 |
| 54 | 1.0 | 2.3 | 8.7 | 29.0 | 3.3 |
| 55 | 0.2 | 0.6 | 1.3 | 8.0 | 6.2 |
| 56 | 0.5 | 0.9 | 3.6 | 7.0 | 1.9 |
| 57 | 0.4 | 0.5 | 3.3 | 5.0 | 1.5 |
| 58 | 1.6 | 1.5 | 15.1 | 18.0 | 1.2 |
| 59 | 0.3 | 0.5 | 2.1 | 4.0 | 1.9 |
| 60 | 0.8 | 4.7 | 8.3 | 65.0 | 7.8 |
| Mean | 2.0 | 5.8 | 30.0 | 97.4 | 3.3 |
| S.D. | 3.36 | 10.9 | 62.9 | 209.4 | 3.3 |
| Median | 0.8 | 1.5 | 8.3 | 18.0 | 2.2 |
| CTP-347 10 mg twice daily | |||||
| Patient no. | |||||
| 85 | 1.5 | 16.9 | 11.4 | 164.0 | 14.4 |
| 86 | 0.8 | 1.6 | 5.3 | 11.0 | 2.1 |
| 88 | 0.2 | 0.9 | 0.6 | 6.0 | 10.0 |
| 89 | 0.6 | 1.3 | 2.0 | 11.0 | 5.5 |
| 90 | 2.3 | 33.2 | 20.0 | 318.0 | 15.9 |
| 91 | 0.5 | 5.2 | 4.0 | 50.0 | 12.5 |
| 92 | 0.2 | 1.0 | 1.1 | 5.0 | 4.5 |
| Mean | 0.8 | 8.6 | 6.3 | 80.7 | 12.8 |
| S.D. | 0.8 | 12.3 | 7.1 | 119.2 | 16.8 |
| Median | 0.8 | 5.2 | 5.3 | 50.0 | 9.4 |
| CTP-347 20 mg daily | |||||
| Patient no. | |||||
| 61 | 2.0 | 6.2 | 21.7 | 72.0 | 3.3 |
| 62 | 1.5 | 29.8 | 20.4 | 523.0 | 25.6 |
| 63 | 12.1 | 15.6 | 145.1 | 233.0 | 1.6 |
| 64 | 0.6 | 1.7 | 4.7 | 24.0 | 5.1 |
| 66 | 0.8 | 7.9 | 11.8 | 112.0 | 9.5 |
| 67 | 3.4 | 11.6 | 32.6 | 136.0 | 4.2 |
| 69 | 2.6 | 33.4 | 33.4 | 597.0 | 17.9 |
| 71 | 3.8 | 37.2 | 37.5 | 585.0 | 15.6 |
| 72 | 1.2 | 9.0 | 14.0 | 134.0 | 9.6 |
| Mean | 3.1 | 16.9 | 35.7 | 268.4 | 7.5 |
| S.D. | 3.6 | 13.1 | 42.5 | 232.6 | 5.5 |
| Median | 2.0 | 11.6 | 21.7 | 136.0 | 6.3 |
| CTP-347 40 mg daily | |||||
| Patient no. | |||||
| 74 | 1.0 | 31.7 | 11.5 | 489.0 | 42.5 |
| 75 | 1.3 | 24.0 | 13.7 | 342.0 | 25.0 |
| 77 | 2.4 | 75.4 | 28.9 | 1231.0 | 42.6 |
| 78 | 14.7 | 124.2 | 220.0 | 2170.0 | 9.9 |
| 79 | 4.7 | 57.9 | 60.3 | 963.0 | 16.0 |
| 81 | 10.5 | 132.1 | 132.0 | 2090.0 | 15.8 |
| 82 | 1.1 | 39.3 | 15.2 | 562.0 | 37.0 |
| 83 | 9.5 | 122.8 | 112.4 | 1924.0 | 17.1 |
| 84 | 5.9 | 59.7 | 66.8 | 1004.0 | 15.0 |
| Mean | 5.7 | 74.1 | 73.4 | 1197.2 | 16.3 |
| S.D. | 4.9 | 42.2 | 70.2 | 707.2 | 10.1 |
| Median | 4.7 | 59.7 | 60.3 | 1004.0 | 16.7 |
ND, not determined; PK, pharmacokinetics.
↵a Day 14 AUCss/Day 1 AUC0–last.