Table 4.
Plasma pharmacokinetic parameters
| Cohort | CC-486 dose (mg) |
Romidepsin dose (mg/m2) |
Cmax (ng/mL) |
Tmax (h) |
AUCINF (ng*h/mL) |
t1/2 (h) |
Cl/F or Cl (L/h) |
V/F or V (L) |
|---|---|---|---|---|---|---|---|---|
| 5-azacitidine | ||||||||
| 1 | 200 | 8 | 324.0 ± 157.2 (3) |
1.00 (0.25 – 1.00; 3) |
537, 538 (2) |
0.55, 0.59 (2) |
372, 373 (2) |
293, 319 (2) |
| 2 and 3 | 300 | 8 | 225.7 ± 130.2 (14) |
1.08 (0.42 – 3.40; 14) |
523 ± 269 (10) |
0.62 ± 0.16 (10) |
922 ± 892 (10) |
731 ± 557 (10) |
| Romidepsin | ||||||||
| Any | Any | 8 | 455.1 ± 254.9 (16) |
4.00 (3.00–4.50; 16) |
1998 ± 1259 (16) |
13.4 ± 4.5 (16) |
10.7 ± 5.7 (16) |
15.7 ± 6.1 (16) |
Data are presented in the table as mean values ± SD (n). T max is presented as median (range; n). If n<3, the actual values are reported.
Abbreviations: AUCINF area under the plasma concentration-time curve to infinity; Cl systemic clearance; Cl/F apparent systemic clearance; Cmax, peak plasma concentration; Tmax, time to peak concentration; t1/2 half life; V volume of distribution; V/F apparent volume of distribution.