Table 4. Assessment of potential pharmacokinetic drug interactions.
| Dosing regime | N | Cmax/Cmax, ss (ng ml−1) | AUC/AUCss (ng.h ml−1) |
|---|---|---|---|
| Saracatinib alone | 9 | 590 (38.4) | 10600 (43.8) |
| Saracatinib+carboplatin+paclitaxel | 9 | 545 (42.2) | 9990 (35.5) |
| Ratio of saracatinib in combination/alone | 9 | 0.923 (0.675–1.25) | 0.940 (0.774–1.23) |
| Carboplatina without saracatinib | 4 | 33600 (20.4) | 64933 (24.8) |
| Carboplatina in combination with saracatinib | 4 | 36500 (15.5) | 73867 (16.0) |
| Ratio of carboplatina with/without saracatinib | 4 | 1.087 (0.898–1.53) | 1.14 (0.921–1.67) |
| Paclitaxelb without saracatinib | 6 | 2970 (35.4) | 9850 (22.8) |
| Paclitaxelb in combination with saracatinib | 6 | 2840 (22.2) | 10100 (20.9) |
| Ratio of paclitaxelb with/without saracatinib | 6 | 0.957 (0.682–1.82) | 1.02 (0.871–1.51) |
Abbreviations: AUCss=area under the plasma concentration–time curve during any dosing interval at steady state (for saracatinib); AUC=area under the plasma concentration–time curve (for carboplatin and paclitaxel); Cmax, ss=maximum plasma concentration at steady state (for saracatinib); Cmax=maximum plasma concentration (for carboplatin and paclitaxel); N=number subjects used to calculate parameters. Parameters are expressed as geometric mean (coefficient of variation, %); ratios are geometric mean (range).
a
In combination with paclitaxel.
b
In combination with carboplatin.