TABLE 4.
PK changes (geometric mean, CV%) of crizotinib, alectinib, and lorlatinib under DDIs.
| Clinical study | Parameters | CRI only (150 mg OD) | CRI + ketoconazole (+200 mg BID) | Predicted ratio | Observed ratio |
|---|---|---|---|---|---|
| Xu et al. (2015b) | AUC0-inf (ng·h·mL-1) | 1590 (33) | 5452 (43) | 3.43 | 3.16 |
| Cmax (ng/mL) | 70 (28) | 100 (33) | 1.43 | 1.44 | |
| Parameters | CRI only (250 mg OD) | CRI + rifampin (+600 mg OD) | Predicted ratio | Observed ratio | |
| AUC0-inf (ng·h·mL-1) | 2943 (30) | 388 (33) | 0.13 | 0.18 | |
| Cmax (ng/mL) | 121 (19) | 60 (33) | 0.50 | 0.31 | |
| Zhao et al. (2020) | Parameters | ALE only (300 mg OD) | ALE + posaconazole (+400 mg BID) | Predicted ratio | Observed ratio |
| AUC0-inf (ng·h·mL-1) | 3280 (32) | 7007 (49) | 2.14 | 1.75 | |
| Cmax (ng/mL) | 136 (44) | 182 (34) | 1.34 | 1.18 | |
| Parameters | ALE only (600 mg OD) | ALE + rifampin (+600 mg OD) | Predicted ratio | Observed ratio | |
| AUC0-inf (ng·h·mL-1) | 5146 (45) | 999 (47) | 0.19 | 0.27 | |
| Cmax (ng/mL) | 260 (28) | 116 (31) | 0.45 | 0.49 | |
| Parameters | LOR only (100 mg OD) | LOR + itraconazole (+200 mg OD) | Predicted ratio | Observed ratio | |
| Patel et al. (2020) | AUC0-inf (ng·h·mL-1) | 5580 (21) | 8287 (39) | 1.49 | 1.41 |
| Cmax (ng/mL) | 455 (18) | 649 (37) | 1.43 | 1.24 | |
| Parameters | LOR only (100 mg OD) | LOR + rifampin (+600 mg OD) | Predicted ratio | Observed ratio | |
| Chen et al. (2020) | AUC0-inf (ng·h·mL-1) | 7021 (23) | 1726 (58) | 0.25 | 0.15 |
| Cmax (ng/mL) | 692 (32) | 374 (29) | 0.54 | 0.24 |