Table 5.
Plasma Pharmacokinetic Parameters1 of Veliparib or Temozolomide when Administered Alone and in Combination
| Veliparib Dose (mg) | Temozolomide Dose (mg/m2/day) | Alone or in Combination | Cmax (μg/mL) | tmax (h) | AUCINF or Tau (μg*h/mL) | t1/2 (h) | Cl/F (L/h) | V/F (L) |
|---|---|---|---|---|---|---|---|---|
| Veliparib Pharmacokinetics | ||||||||
| 20 | 150 or 200 | Alone | 0.09±0.03 (4) | 2.8 (0.5–4.0; 4) | 0.7±0.4 (3) | 5.9±0.4 (3) | 33.2±18.4 (3) | 285±175 |
| Combination | 0.14±0.006 (3) | 2.0 (1.0–4.0; 3) | 0.9±0.1 (3) | 5.6±2.1 (3) | 22.9±3.6 (3) | 180±49 (3) | ||
| 40 | 200 | Alone | 0.45 (1) | 2.0 (1) | 4.7 (1) | 7.3 (1) | 8.6 (1) | 90 (1) |
| Combination | n/a | n/a | n/a | n/a | n/a | n/a | ||
| 80 | 200 | Alone | 0.26, 0.98 (2) | 1.0, 1.5 (2) | 3.1, 5.1 (2) | 3.2, 8.9 (2) | 15.6, 25.6 (2) | 72, 328 (2) |
| Combination | 0.69, 1.0 (2) | 2.0, 2.0 (2) | 4.6, 8.1 (2) | 5.3, 6.9 (2) | 9.9, 17.4 (2) | 76, 173 (2) | ||
| 120 | 200 | Alone | 0.74±0.21 (10) | 1.5 (0.5–6.0; 10) | 6.3±1.7 (1) | 6.7±3.2 (10) | 20.2±4.9 (10) | 181±50 (10) |
| Combination | 1.2±0.25 (8) | 2.0 (1.5–4.0; 8) | 8.4±1.8 (8) | 9.1±8.0 (8) | 15.0±3.6 (8) | 191±165 (8) | ||
| 150 | 200 | Alone | 1.0±0.31 (16) | 1.5 (0.5–4.0; 16) | 10.4±7.5 (16) | 9.0±7.3 (16) | 18.4±7.5 (16) | 190±72 (16) |
| Combination | 1.5±0.75 (12) | 1.3 (0.3–4.0; 12) | 12.4±6.1 (10) | 5.3±1.7 (10) | 14.6±6.8 (10) | 109±45 (10) | ||
| 200 | 200 | Alone | 2.5±0.99 (4) | 1.8 (1.0–2.0; 4) | 15.1±5.1 (4) | 4.1±1.2 (4) | 14.6±5.1 (4) | 84±26 (4) |
| Combination | 3.9±3.0 (3) | 1.5 (1.0–2.0; 3) | 14.5±4.1 (3) | 3.6±2.8 (3) | 14.6±4.1 (3) | 77±59 (3) | ||
| Temozolomide Pharmacokinetics | ||||||||
| 20 | 150 | Alone | 5.9, 10.2 (2) | 1.0, 4.0 (2) | 27.4, 33.8 (2) | 1.9, 2.3 (2) | Pred. 10.3, 13.2 (2) Obs. 8.6, 13.1 (2) |
Pred. 32, 37 (2) Obs. 29, 35 (2) |
| Combination | 6.3, 8.3 (2) | 1.0, 2.0 (2) | 25.6, 36.0 (2) | 1.6, 2.9 (2) | 8.1, 14.1 (2) | 33, 33 (2) | ||
| 20–200 | 200 | Alone | 13.1±5.3 (34) | 1.0 (0.3–4.0; 34) | 41.8±12.4 (34) | 1.9±0.2 (34) | Pred. 11.1±1.32 (34) Obs. 9.2±3.2 (34) |
Pred. 31±3.2 (34) Obs. 25±9.1 (34) |
| Combination | 12.0±3.8 (25) | 1.0 (0.3–4.0, 25) | 37.4±10.5 (25) | 1.9±0.4 (25) | 10.1±2.7 (25) | 28±10 (25) | ||
1
Data were obtained from n patients and are presented in the table as mean values ± SD (n). tmax is presented as median (range; n). If n<3, the actual values are reported.