Interacting Drug | Control Group | Treatment Group | Fold Increasea | ||||||
---|---|---|---|---|---|---|---|---|---|
Cmax | AUC0–∞ | t1/2,z | Cmax | AUC0–∞ | t1/2,z | CmaxR | AUCR | ||
ng/ml | ng⋅h/ml | h | ng/ml | ng⋅h/ml | h | ratio | ratio | ||
Ketoconazole | Observed | 66 (35) | 1260 (25) | 37 (12) | 94 (20) | 3986 (25) | 55 (11) | 1.4 | 3.2 |
Predicted (on)b | 57 (35) | 1422 (47) | 51 (22) | 89 (32) | 4896 (41) | 113 (30) | 1.6 | 3.4 | |
P/Oc | 0.87 | 1.1 | 1.4 | 0.95 | 1.2 | 2.1 | 1.1 | 1.1 | |
Predicted (off)b | 56 (35) | 1335 (45) | 50 (21) | 89 (32) | 4764 (41) | 111 (29) | 1.6 | 3.6 | |
On/Offd | 1.0 | 1.1 | 1.0 | 1.0 | 1.0 | 1.0 | 0.99 | 0.96 | |
Rifampin | Observed | 102 (33) | 2192 (27) | 33 (21) | 32 (33) | 397 (26) | 48 (12) | 0.31 | 0.18 |
Predicted (on)b | 95 (35) | 2499 (48) | 55 (23) | 29 (56) | 369 (69) | 33 (16) | 0.31 | 0.15 | |
P/Oc | 0.93 | 1.1 | 1.7 | 0.91 | 0.93 | 0.69 | 0.97 | 0.82 | |
Predicted (off)b | 94 (35) | 2256 (45) | 53 (22) | 28 (59) | 343 (69) | 33 (16) | 0.30 | 0.15 | |
On/Offd | 1.0 | 1.1 | 1.0 | 1.0 | 1.1 | 1.0 | 1.0 | 0.97 |
↵a Fold-increase in Cmax and AUC0–∞ of the treatment group (crizotinib with ketoconazole or rifampin) relative to control group (crizotinib alone).
↵b The simulation results with (on) and without (off) crizotinib DDI parameters.
↵c Ratio of the predicted to observed results.
↵d Ratio of the predicted results on over off.