Table 4.
Pharmacokinetic parameters of belinostat (Bel) following administration of Bel alone (cycle 1 day 4) or in combination with doxorubicin (cycle 1 day 5).
| Occasion | 600 mg/m2 Bel + 50 mg/m2 doxorubicin | 600 mg/m2 Bel + 75 mg/m2 doxorubicin | 800 mg/m2 Bel + 75 mg/m2 doxorubicin | 1000 mg/m2 Bel + 75 mg/m2 doxorubicin | ||||
|---|---|---|---|---|---|---|---|---|
| Day 4 | Day 5 | Day 4 | Day 5 | Day 4 | Day 5 | Day 4 | Day 5 | |
| (N = 3) | (N = 3) | (N = 7) | (N = 6) | (N = 8) | (N = 6) | (N = 21) | (N = 19) | |
| AUC0–tlast (ng·h/mL) | 10900 (16.2) | 10400 (22.3) | 9670 (40.0) | 10400 (24.7) | 12200 (28.5) | 14600 (26.0) | 23100 (35.4) | 22100 (43.2) |
| C max (ng/mL) | 21100 (13.6) | 18300 (36.2) | 16800 (69.2) | 17400 (45.1) | 21400 (44.9) | 26400 (30.0) | 41100 (35.0) | 37000 (59.1) |
| t max a (h) | 0.533 (0.500–0.550) | 0.567 (0.550–0.583) | 0.567 (0.500–0.783) | 0.517 (0.467–0.667) | 0.533 (0.500–0.583) | 0.533 (0.483–0.583) | 0.617 (0.500–0.750) | 0.633 (0.517–1.60) |
| t last a (h) | 24.5 (22.4–24.6) | 17.0 (17.0–20.1) | 24.0 (8.55–24.5) | 24.5 (16.2–24.7) | 23.7 (8.47–24.6) | 15.1 (8.50–24.6) | 8.65 (1.05–24.0) | 8.72 (8.50–24.7) |
| AUC0–tlast (norm) | 18.2 (16.2) | 17.3 (22.3) | 16.1 (40.0) | 17.3 (24.7) | 15.3 (28.5) | 18.2 (26.0) | 23.1 (35.4) | 22.1 (43.2) |
| C max (norm) | 35.2 (13.6) | 30.5 (36.2) | 28.0 (69.2) | 28.9 (45.1) | 26.8 (44.9) | 32.9 (30.0) | 41.1 (35.0) | 37.0 (59.1) |
| t 1/2 (h) | NC (NC) | 2.53e (NC) | 3.77b (136.4) | 4.83b (45.7) | 1.91c (129.8) | 2.14c (114.9) | 1.48d (71.3) | 2.13 (119.4) |
| CL (L/h) | NC (NC) | 106e (NC) | 129b (61.8) | 111b (12.1) | 127c (40.5) | 91.0c (18.1) | 81.6d (39.9) | 85.2 (41.0) |
| V ss (L) | NC (NC) | 72.8e (NC) | 149b (365.2) | 90.8b (7.1) | 107c (195.5) | 58.3c (29.5) | 51.0d (45.1) | 57.6 (61.8) |
N: number of patients studied.
aMedian (min–max).
(norm): normalised for dose.
NC: not calculable.
b N: 3.
c N: 4.
d N: 18.
e N: 1; individual parameter presented.