Table 5. Non-compartmental pharmacokinetic parameter estimates.
Noncompartmental PK parameters were estimated for each individual on study using noncompartmental analysis in WinNonlin. Cohorts with equivalent doses were combined.
| Dose Level (Bolus+Infusion mg/m2) |
No. pts | K 1/hr |
T1/2 hr |
Tmax hr |
Cmax µM |
Conc0.5µM | Conc 4.5 µM |
AUCO-∞ hr x µM |
V2 L/m2 |
CL L/hr/m2 |
|---|---|---|---|---|---|---|---|---|---|---|
| −1, −1B (20+20) | 8 | 0.10 ± 0.08 | 14.8 ± 11.3 | 0.98 ± 1.00 | 0.94 ± 0.22 | 0.91 ± 0.26 | 0.75 ± 0.24 | 7.9 ± 4.2 | 117 ± 99 | 6.1 ± 2.5 |
| 1, 1B (30+30) | 6 | 0.07 ± 0.03 | 11.7 ± 4.6 | 1.09 ± 1.07 | 1.62 ± 0.46 | 1.59 ± 0.49 | 1.17 ± 0.44 | 13.2 ± 3.4 | 198 ± 82 | 11.9 ± 3.0 |
| 2, 2B (30+45) | 9 | 0.06 ± 0.02 | 15.6 ± 11.0 | 1.35 ± 1.50 | 1.79 ± 0.83 | 1.65 ± 0.85 | 1.41 ± 0.94 | 14.3 ± 6.8 | 307 ± 155 | 15.3 ± 5.8 |
| 3 (30+60) | 9 | 0.06 ± 0.02 | 13.8 ± 6.1 | 3.68 ± 1.92 | 1.92 ± 1.07 | 1.15 ± 0.54 | 1.78 ± 1.13 | 16.6 ± 8.6 | 309 ± 168 | 16.5 ± 7.0 |
| 4 (30+75) | 2 | 0.05 ± 0.01 | 14.1 ± 2.4 | 4.53 ± 0.00 | 2.71 ± 1.08 | 1.04 ± 0.05 | 2.71 ± 1.07 | 20.8 ± 5.6 | 260 ± 28 | 13.1 ± 3.6 |
| All | 34 | 0.07 ± 0.05 | 14.2 ± 8.4 | 2.02 ± 1.87 | 1.65 ± 0.86 | 1.30 ± 0.63 | 1.39 ± 0.90 | 13.6 ± 7.0 | 241 ± 149 | 12.7 ± 6.3 |
The table lists mean values ± standard deviations. N, number of patients in each group; k, elimination rate constant; T1/2, elimination half-life; Tmax, time of observed maximum concentration; cmax, maximum observed concentration; Conc0.5, observed concentration at the end of the bolus dose; C4.5, observed concentration at the end of the 4-hour infusion; AUC0-∞, observed area under the curve; Vz, volume of distribution; CL, clearance.