Table 3.
Mean Pharmacokinetic Parameters for All Cycles of MLN2704 on Two- and Three-Week Schedules
| Dose (mg/m2) | No. of Patients | Apparent half-life(h) | Cmax (μg/mL) | AUC0-∞ (μg*h/mL) | Apparent clearance mL/(h*m2) | ||||
|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||
| Mean | SD | Mean | SD | Mean | SD | Mean | SD | ||
| Two-week Schedule | |||||||||
| 120 | 3 | 55.7 | 4.9 | 52.4 | 12.3 | 2692 | 670 | 51.1* | 20.2** |
| 168 | 3 | 52.7 | 0.6 | 89.6 | 12.4 | 4858 | 671 | 35.6 | 5.4 |
| 236 | 3 | 59.2 | 9.9 | 138.1 | 16.3 | 9535 | 1542 | 26.5 | 6.4 |
| 330 | 6 | 59.3 | 8.0 | 214.9 | 13.3 | 13210 | 1364 | 26.1 | 2.8 |
| Three-week Schedule | |||||||||
| 330 | 14 | 59.9 | 0.7 | 163.6 | 8.6 | 10359 | 356 | 33.5 | 0.4 |
| 462 | 4 | 65.8 | 1.1 | 273.3 | 15.9 | 17658 | 2048 | 26.8 | 3.4 |
AUC0-∞ = area under the concentration time curve from time zero extrapolated to infinity; Cmax = maximum serum concentrations; SD = standard deviation.
**
Result driven by patient 001-001’s observed rate of clearance during cycle 1. When removed, the mean clearance for patients at the 120mg/m2 dose is 43.0 +/− 5.1 mL/(h*m2).