Pharmacokinetic and pharmacodynamic parameters of DPC 333 after single oral administration to healthy human volunteers
Parameter | 15 mg (n = 6) | 25 mg (n = 6) | 40 mg (n = 6) | 80 mg (n = 12) | 120 mg (n = 6) | 225 mg (n = 6) | 345 mg (n = 6) | 530 mg (n = 6) |
|---|---|---|---|---|---|---|---|---|
| AUC (nM · h) | 341.9 ± 86.3 | 675.9 ± 223.1 | 1179.0 ± 244.6 | 3202.2 ± 957.1 | 4773.6 ± 1436.5 | 7888.4 ± 1507.8 | 23,598.4 ± 5220.5 | 30,762.2 ± 8718.5 |
| Cmax (nM) | 133.6 ± 45.1 | 303.2 ± 132.0 | 505.0 ± 148.8 | 1420.3 ± 450.5 | 1941.5 ± 404.7 | 3139.5 ± 510.8 | 11,001.7 ± 4415.5 | 13,761.0 ± 4310.8 |
| Tmax (h)a | 0.75 (0.5-1.0) | 0.5 (0.5-1.0) | 0.5 (0.25-1.0) | 0.5 (0.5-1.0) | 0.5 (0.5-1.0) | 0.75 (0.5-1.0) | 0.75 (0.25-1.0) | 0.5 (0.5-1.0) |
| t½ (h)b | 2.18 ± 0.21 | 2.86 ± 0.86 | 3.41 ± 0.67 | 4.05 ± 0.51 | 4.89 ± 0.99 | 5.53 ± 0.88 | 6.39 ± 0.73 | 6.04 ± 0.58 |
| C12 h (nM) | 2.09 ± 0.79 | 4.41 ± 2.08 | 6.36 ± 1.03 | 20.4 ± 6.60 | 30.26 ± 12.74 | 49.03 ± 9.37 | 152.8 ± 32.2 | 167.3 ± 43.9 |
| % inhibition of TNF-α release | 39.4 ± 16.0 | 51.8 ± 15.8 | 58.1 ± 25.8 | 82.2 ± 10.1 | 81.6 ± 7.3 | 91.0 ± 3.7 | 96.9 ± 1.2 | 96.1 ± 0.02 |
| Range | (25.5-58.5) | (30.9-67.7) | (27.1-92.1) | (57.1-100) | (76.6-93.4) | (86.4-94.8) | (95.6-98.5) | (93.9-98.2) |
| Median Tmax (h) | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 |