Table 3.
Continuous dosing study: TAK-683 plasma PK parameters for days 1, 2 and 14
| Geometric mean (%CV) | |||||
|---|---|---|---|---|---|
| Cohort 1 (n = 5) | Cohort 2 (n = 5) | Cohort 3 (n = 5) | Cohort 4 (n = 5) | Cohort 5 (n = 5) | |
| 0.01 mg | 0.03 mg | 0.1 mg | 0.3 mg | 2.0 mg | |
| Plasma | |||||
| Day 1 (s.c. bolus dose) | |||||
| Cmax (pg ml−1) | 173.7 (47.98) | 538.3 (18.12) | 1650 (11.34) | 7 824 (17.36) | 7 139 (23.30) |
| tmax (h), median, (range) | 0.25 (0.25–0.52) | 0.28 (0.25–0.52) | 0.50 (0.25–0.75) | 0.50 (0.28–0.75) | 0.50 (0.27–0.53) |
| AUC(0,24 h) (pg ml−1 h) | 495.6 (29.97) | 1579 (32.90) | 5760 (12.79) | 22 954 (2.30) | 19 364 (24.05) |
| AUC(0, ∞) (pg ml−1 h) | 558.2 (21.65) | 1617 (34.50) | 6059 (12.33) | 23 476 (2.63) | 20 272 (22.85) |
| t1/2 (h), median, (range) | 4.32 (3.43–9.36) | 5.32 (3.38–7.46) | 6.64 (5.68–8.27) | 5.45 (4.81–5.99) | 5.57 (4.08–10.40) |
| Day 2 (s.c. infusion) | |||||
| Cavg (pg ml−1) | 6.32 (20.31) | 19.54 (48.03) | 67.24 (25.68) | 224.9 (10.21) | 1 423 (23.62) |
| AUC(0,24 h) (pg ml−1 h) | 151.8 (20.29) | 469.0 (48.10) | 1614 (25.73) | 5 398 (10.21) | 34 163 (23.62) |
| Day 14 (s.c. infusion) | |||||
| Cavg (pg ml−1) | 4.14 (78.27) | 15.05 (38.89) | 55.10 (24.71) | 206.7 (22.83) | 677.5 (28.76) |
| AUC(0,24 h) (pg ml−1 h) | 99.83 (77.17) | 361.3 (38.76) | 1323 (24.68) | 4 960 (22.83) | 16 259 (28.76) |
| t1/2 (h), median, (range) | 3.44 (3.44–3.44) | 2.59 (1.18–4.00) | 3.67 (2.07–5.46) | 6.69 (4.11–10.80) | 14.26 (10.80–17.94) |
AUC(0, ∞), area under the plasma concentration–time curve from time 0 to infinity; AUC(0,24 h), area under the plasma concentration-time curve from time 0 to 24 h; Cmax, maximum observed plasma concentration; Cavg, Average observed plasma concentration over 24 h; t1/2, terminal half life, n(2)/λz; tmax, time to reach Cmax.