Table 4.
Pharmacokinetic parameters for RO6839921 (prodrug)
| Dose, mg | Day 1 | Day 5 | Ratio (day 5/day 1) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| tmax, h | Cmax, ng/mL | AUC0–24, h•ng/mL | tmax, h | Cmax, ng/mL | AUC0–24, h•ng/mL | t1/2, h* | Cmax, ng/mL | AUC0–24, h•ng/mL | ||
| 120 | N | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (SD)† | 1.05 (1.00–2.03) | 19,100 (4970) | 86,200 (27,700) | 1.03 (1.00–1.18) | 18,000 (5530) | 89,600 (30,000) | 23.0 (26.0) | 0.944 (0.102) | 1.04 (0.10) | |
| CV% | 33.6 | 26.1 | 32.1 | 6.7 | 30.7 | 33.4 | 113 | 10.8 | 9.9 | |
| 200 | N | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 |
| Mean (SD)† | 1.12 (1.00–1.98) | 27,000 (4070) | 126,000 (38,400) | 1.03 (1.00–2.08) | 32,400 (13,400) | 164,000 (40,700) | 20.8 (9.85) | 1.25 (0.724) | 1.39 (0.46) | |
| CV% | 28.7 | 15.1 | 30.5 | 33.4 | 41.4 | 24.7 | 47.5 | 57.7 | 33.1 | |
| 250 | N | 8 | 8 | 8 | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (SD)† | 1.08 (1.02–1.92) | 76,500 (84,400) | 241,000 (85,400) | 1.05 (1.00–2.00) | 43,500 (12,500) | 258,000 (79,500) | 50.0 (28.4) | 0.832 (0.368) | 1.14 (0.37) | |
| CV% | 26.2 | 110 | 35.4 | 36.1 | 28.8 | 30.9 | 56.9 | 44.3 | 32.0 | |
| 300 | N | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 | 5 |
| Mean (SD)† | 2.00 (1.03–2.08) | 66,700 (46,900) | 304,000 (89,500) | 1.98 (1.02–2.00) | 41,700 (7910) | 335,000 (93,100) | 60.3 (49.8) | 0.762 (0.252) | 1.1 (0.14) | |
| CV% | 33.1 | 70.4 | 29.4 | 28.5 | 19.0 | 27.8 | 82.5 | 33.1 | 12.3 | |
AUC0–24, 24-h area under the plasma concentration-time curve; Cmax, maximum concentration; CV, coefficient of variation; tmax, time to maximum concentration
*t½ (terminal half-life) cannot be determined for day 1 due to a limited sampling schedule
†Median (min-max) is given for tmax