Table IX.
Vorinostat pharmacokinetics parameters.
| PK parameter | 100 mg bid days 6–21 (n = 4) | 200 mg bid days 6–21 (n = 4) | 200 mg tid days 6–21 (n = 8) |
|---|---|---|---|
| Sequential schedule | |||
| Mean Cmax (ng/mL) (SD) | 116.8 (82.5) | 125.5 (56.1) | 263.4 (170.8) |
| Mean AUCt (ng·h/mL) (SD) | 276.3 (87.9) | 555.9 (354.7) | 743.2 (421.4) |
| Mean AUCinf (ng·h/mL) (SD) | 352.1 (57.9) | 974.1 (599.2) | 910.4 (633.9) |
| Mean t½ (h) (SD) | 1.23 (0.02) | 3.34 (0.66) | 1.65 (1.02) |
| Mean CL/F (L/min) (SD) | 4.80 (0.79) | 5.57 (5.26) | 5.89 (4.48) |
| 100 mg bid days 1–21 |
200 mg bid days 1–21 |
200 mg tid days 1–14 |
||||
|---|---|---|---|---|---|---|
| Day 4 (n = 3) | Day 15 (n = 1) | Day 4 (n = 10) | Day 15 (n = 7) | Day 4 (n = 7) | Day 15 (n = 0) | |
| Concurrent schedule | ||||||
| Mean Cmax (ng/mL) (SD) | 150.8 (40.5) | 226.3 | 251.5 (96.0) | 245.6 (115.3) | 352.9 (110.9) | NA |
| Mean AUCt (ng·h/mL) (SD) | 399.9 (127.1) | 607.5 | 733.8 (362.9) | 778.5 (401.7) | 1062.9 (262.7) | NA |
| Mean AUCinf (ng·h/mL) (SD) | 406.7 (121.4) | 608.6 | 930.0 (357.8) | 1007.2 (649.1) | 1239.4 (403.5) | NA |
| Mean t½ (h) (SD) | 1.04 (0.52) | 0.62 | 1.94 (0.64) | 2.34 (1.05) | 2.68 (1.93) | NA |
| Mean CL/F (L/min) (SD) | 4.35 (1.26) | 2.74 | 4.02 (1.30) | 4.70 (2.45) | 2.86 (0.81) | NA |
PK, pharmacokinetics; Cmax, maximum plasma concentration; SD, standard deviation; AUCt, area under the plasma decitabine concentration versus time curve to the last sampling time; AUCinf, area under the plasma decitabine concentration versus time curve from zero to infinity; t½, terminal half-life; CL/F, oral clearance.