Table 3. Effect of carboplatin on oral rucaparib PK parameters and of chemotherapy on i.v. rucaparib PK parameters.
|
Ratio of rucaparib PK parameters,a
mean (CV%) |
||
|---|---|---|
| Cmax | AUC0–24 | |
| Oral rucaparib | ||
| Carboplatin dose | ||
| AUC3 (n=15) | 1.25 (46) | 1.27 (37) |
| AUC4 (n=3) | 0.928 (24) | 1.15 (51) |
| AUC5 (n=11) | 1.14 (59) | 1.00 (48) |
| Overall (n=29) | 1.18 (49) | 1.15 (87) |
| Ratio of rucaparib PK parameters,b mean (CV%) | ||
| Cmax | AUC0–24 | |
|
i.v. rucaparib | ||
| Chemotherapy | ||
| Carboplatin (n=6) | 1.03 (16) | 1.02 (15) |
| Carboplatin+paclitaxel (n=6) | 0.917 (16) | 0.86 (8) |
| Cisplatin+pemetrexed (n=8) | 0.853 (42) | 0.959 (20) |
| Epirubicin+cyclophosphamide (n=5) | 0.968 (29) | 0.916 (34) |
Abbreviations: AUC=area under the concentration time curve; AUC0–24=AUC for time 0 to 24 h; Cmax=maximum plasma drug concentration; CV=coefficient of variation; i.v.=intravenous; PK=pharmacokinetic.
a
Ratio of rucaparib PK parameter on day 1/day −5 with single oral dose of rucaparib (80, 120, 180, 240, and 360 mg) on day −5 and single oral dose of rucaparib (80, 120, 180, 240, and 360 mg) followed 1.5 h later with 30 min i.v. infusion of carboplatin (AUC3, AUC4, or AUC5) on day 1.
b
Ratio of rucaparib PK parameter on day 1/day −10 with i.v. dose of rucaparib (12, 18, or 24 mg) on day −10 and i.v. rucaparib plus i.v. chemotherapy on day 1; for AUC4, n=2 for AUC ratio; for overall, n=28 for AUC ratio.