Table 5.
Pharmacokinetic parameters for the active principle (idasanutlin)
| 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 | 1 | 6 | 6 | 6 | 4 | 6 | 6 |
| Mean (SD)† | 6.24 (5.92–8.08) | 2840 (545) | 55,000 | 4.48 (3.02–8.00) | 4920 (1770) | 95,300 (37,100) | 29.3 (11.3) | 1.73 (0.50) | 1.76 (0.55) | |
| CV% | 12.4 | 19.2 | – | 46.7 | 36.0 | 38.9 | 38.4 | 29.0 | 31.1 | |
| 200 | N | 7 | 7 | 3 | 7 | 7 | 7 | 6 | 7 | 7 |
| Mean (SD)† | 5.78 (1.93–7.93) | 3540 (1230) | 62,100 (16,500) | 4.00 (2.98–7.82) | 6850 (3000) | 135,000 (63,100) | 31.2 (9.9) | 1.91 (0.52) | 2.02 (0.39) | |
| CV% | 39.6 | 34.9 | 26.5 | 38.5 | 43.8 | 46.8 | 31.6 | 27.1 | 19.5 | |
| 250 | N | 8 | 8 | 4 | 6 | 6 | 6 | 6 | 6 | 6 |
| Mean (SD)† | 6.77 (3.00–8.60) | 4860 (371) | 93,000 (9930) | 3.08 (2.00–5.95) | 8970 (2510) | 166,000 (41,000) | 26.8 (7.01) | 1.82 (0.42) | 1.79 (0.30) | |
| CV% | 39.4 | 7.7 | 10.7 | 38.3 | 28.0 | 24.7 | 26.6 | 23.1 | 16.8 | |
| 300 | N | 5 | 5 | 2 | 5 | 5 | 5 | 5 | 5 | 5 |
| Mean (SD)† | 6.08 (4.00–7.92) | 6120 (1030) | 101,000 (7910) | 5.92 (1.98–6.02) | 11,500 (3610) | 209,000 (64,300) | 34.3 (7.7) | 1.86 (0.33) | 1.83 (0.26) | |
| CV% | 24.9 | 16.8 | 7.86 | 42.5 | 31.4 | 30.8 | 22.5 | 17.9 | 14.4 | |
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