Table 5. Plasma pharmacokinetic parameters1 of veliparib when combined with topotecan and carboplatin.
| Dose | Single or Multiple Dose | Cmax (ng/mL) | tmax (h) | AUCINF or Tau (µg*h/mL) | t1/2 (h) | Cl/F (L/h) | V/F (L) |
|---|---|---|---|---|---|---|---|
| 10 mg | Single | 74.6 ± 33.0 (27) | 2.0 (0.3 - 8.1; 27) | 525 ± 204 (23) | 5.5 ± 3.5 (23) | 27.7 ± 9.3 (23) | 225 ± 191 (23) |
| Multiple | 107.0 ± 33.2 (25) | 1.0 (0.5 - 4.0; 25) | 696 ± 210 (25) | 5.8 ± 1.9 (22) | 16.1 ± 4.2 (22) | 132.3 ± 55.1 (22) | |
| 20 mg | Single | 102.2 ± 31.6 (12) | 2.0 (1.0 - 4.1;12) | 849 ± 243 (12) | 4.7 ± 1.1 (12) | 31.7 ± 7.7 (12) | 216 ± 70 (12) |
| Multiple | 182.2 ± 45.5 (13) | 1.0 (0.5 - 4.1;13) | 1244 ± 413 (13) | 5.6 ± 2.8 (11) | 17.7 ± 4.3 (11) | 133 ± 41 (11) | |
| 40 mg | Single | 231.2 ± 128.2 (5) | 1.0 (0.5 - 2.0; 5) | 1474 ± 526 (5) | 4.1 ± 0.9 (5) | 36.4 ± 15.4 (5) | 221 ± 103 (5) |
| Multiple | 363.6 ± 211.6 (5) | 1.1 (0.5 - 4.0; 5) | 1865 ± 570.2 (5) | 4.5 ± 0.7 (4) | 20.5 ± 5.5 (4) | 131 ± 27 (4) | |
| 80 mg | Single | 608.7 ± 260.3 (35) | 1.1 (0.3 - 6.0; 35) | 4057 ± 1278 (30) | 4.7 ± 1.4 (30) | 26.2 ± 7.1 (30) | 173 ± 53 (30) |
| Multiple | 856.8 ± 317.6 (36) | 1.0 (0.5 - 4.0; 36) | 5137 ± 1820 (36) | 4.7 ± 1.5 (26) | 20.2 ± 11.2 (26) | 131 ± 71 (26) | |
| 90 mg | Single | 509.0 ± 100.6 (3) | 1.0 (1.0 - 4.0; 3) | 3042 ± 1319 (3) | 3.2 ± 1.2 (3) | 35.9 ± 10.2 (3) | 154 ± 16 (3) |
| Multiple | 685.0 ± 375.8 (3) | 1.0 (0.5 - 4.1; 3) | 3836 ± 1739 (3) | 3.4, 3.6 (2) | 15.8, 39.7 (2) | 77.1, 206.8 (2) | |
| 100 mg | Single | 1123.5 ± 718.5 (4) | 1.0 (1.0 - 1.0; 4) | 5044 ± 2655 (4) | 5.9 ± 2.4 (4) | 44.9 ± 50.6 (4) | 504 ± 745 (4) |
| Multiple | 1515.8 ± 494.8 (4) | 0.7 (0.5 - 1.0; 4) | 10108 ± 4356 (3) | 3.6 ± 1.0 (3) | 12.9 ± 6.3 (3) | 72 ± 47 (3) | |
| Accumulation Index | 1.88 ± 1.83 (83) | 1.47 ± 1.07 (75) | |||||
1
Data were obtained from patients receiving veliparib orally and 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; AUCTau area under the plasma concentration-time curve during the dosing interval at steady-state; Cl/F apparent systemic clearance; Cmax, peak plasma concentration; tmax, time to peak concentration; t1/2 half life; V/F apparent volume of distribution.