Table IV.
Summary of Vorinostat pharmacokinetic parameters*
| Dose Level† | 230/150 (N=6) | 300/150 (N=5) | 300/200 (N=5) | |
|---|---|---|---|---|
|
| ||||
| VOR | Tmax (hrs) | 2.00 (0.25 – 2.05) | 2.08 (0.53 – 4.25) | 1.02 (0.50 – 4.07) |
| Cmax(ng/ml) | 390 (221 – 655) | 422 (178 – 663) | 578 (200 – 821) | |
| Half-life(hrs) | 2.61 (0.99 – 11.1) | 2.62 (1.12 – 5.30) | 2.80 (2.23 – 5.90) | |
| AUC0-∞ (ng/ml* hr) | 1420 (547 – 2310) | 1790 (1100 – 2180) | 2070 (1280 – 5430) | |
| V/F(L/m2) | 424 (222 – 7050) | 529 (289 – 1460) | 759 (207 – 1260) | |
| Cl/F(L/hr/m2) | 161 (90.9 – 439) | 175 (138 – 296) | 148 (62.6 – 236) | |
|
| ||||
| 4-anilino-4- oxobutanoic acid | Tmax (hrs) | 3.00 (1.92 – 4.08) | 4.00 (1.00 – 4.25) | 2.00 (0.88 – 6.00) |
| Cmax(ng/ml) | 490 (160 – 884) | 814 (588 – 832) | 750 (559 – 984) | |
| Half-life(hrs) | 10.4 (1.81 – 216) | 9.18 (5.56 – 13.5) | 9.19 (6.49 – 11.6) | |
| AUC0-∞ (ng/ml* hr) | 6900 (2460 – 19100) | 7490 (6410 – 9330) | 9590 (7150 – 16600) | |
|
| ||||
| VOR- glucuronide | Tmax (hrs) | 2.00 (0.45 – 2.05) | 2.08 (1.00 – 4.25) | 2.00 (0.88 – 4.07) |
| Cmax(ng/ml) | 1700 (503 – 2720) | 1870 (1310 – 2620) | 1910 (1570 – 3860) | |
| Half-life(hrs) | 2.53 (1.05 – 49.5) | 2.69 (2.04 – 5.18) | 3.25 (2.12 – 4.62) | |
| AUC0-∞ (ng/ml* hr) | 6810 (4260 – 11000) | 6210 (5630 – 14800) | 13200 (5460 – 16200) | |
*
Median values with range in parentheses.
†
SAHA/TEM (mg/m2).