Table 3. Pharmacokinetics of CYT997.
| Dose (mg m−2) | No. of patients | Css (ng ml−1)a | AUC0−t (ng h ml−1)a | Terminal t½ (h)a | CL (l h−1 kg−1)a | Vapp (l kg−1)a |
|---|---|---|---|---|---|---|
| 7 | 3 | 8.5 (4.4) | 178 (68) | 2.8 (0.6) | 0.89 (0.23) | 3.5 (1.0) |
| 14b | 3 | 15.5 (4.9) | 312 (58) | 6.6 (1.2) | 0.93 (0.20) | 7.8 (1.4) |
| 23 | 3 | 22.0 (8.5) | 470 (153) | 4.3 (1.2) | 1.09 (0.39) | 6.3 (0.8) |
| 35b | 3 | 31.2 (9.2) | 782 (221) | NE | 1.04 (0.26) | NE |
| 49b | 3 | 33.5 (3.2) | 1030 (480) | 3.4 (2.4) | 1.16 (0.50) | 4.1 (0.4) |
| 65 | 3 | 67.8 (17.4) | 1370 (280) | 4.2 (1.1) | 1.05 (0.26) | 6.1 (0.3) |
| 86 | 1 | 77.3 | 1780 | 5.4 | 1.07 | 8.3 |
| 114 | 1 | 135 | 2920 | 4.6 | 0.85 | 5.7 |
| 152 | 1 | 110 | 2140 | 3.9 | 1.50 | 8.4 |
| 202 | 1 | 154 | 3630 | 4.5 | 1.36 | 8.7 |
| 269 | 5c | 217 (57) | 4570 (1130) | 5.1 (1.7) | 1.11 (0.23) | 8.2 (3.0) |
| 358 | 2c | 345 (69) | 5640 (2910) | 4.6 (2.3) | 0.99 (0.18) | 6.8 (4.6) |
Abbreviations: Css=concentration at steady state; AUC0−t=area under the CYT997 plasma concentration vs time curve from the start of the infusion until the last quantifiable concentration; CL=clearance; Vapp=apparent volume of distribution; NE, not evaluable.
a
Pharmacokinetic parameters represent the mean (s.d.) for the corresponding dose level.
b
The concentrations in plasma profile for one subject at 14 mg m−2, all three at 35 mg m−2 and one at 49 mg m−2 could not be extrapolated to infinity and, therefore, the number of subjects available for calculation of mean terminal t½ was reduced accordingly.
c
Data were not available on one patient in each of the 269 and 358 mg m−2 dose levels because of early termination of CYT997 infusions.