Clinically observed and PBPK model-predicted pharmacokinetic parameters of bosutinib in healthy subjects after a single oral administration of 500 mg bosutinib with and without repeated coadministration of 400 mg ketoconazole and 600 mg rifampin once daily
Data are expressed as geometric means with percent coefficients of variation in parentheses.
| Precipitant | Analysis | Control Group | Treatment Group | Ratioa | |||
|---|---|---|---|---|---|---|---|
| Cmax | AUC | Cmax | AUC | CmaxR | AUCR | ||
| ng/ml | ng⋅h/ml | ng/ml | ng⋅h/ml | ||||
| Ketoconazole | Observed | 107 (35) | 1980 (35) | 315 (24) | 10,500 (27) | 2.9 | 5.3 |
| Predicted | 83 (42) | 2407 (49) | 314 (31) | 13,698 (37) | 3.8 | 5.7 | |
| P/O | 0.8 | 1.2 | 1.0 | 1.3 | 1.3 | 1.1 | |
| Rifampin | Observed | 109 (26) | 2350 (28) | 15 (42) | 149 (34) | 0.14 | 0.06 |
| Predicted | 83 (42) | 2575 (51) | 8.9 (87) | 145 (91) | 0.11 | 0.06 | |
| P/O | 0.8 | 1.1 | 0.6 | 1.0 | 0.8 | 0.9 | |
↵a Ratios of Cmax and AUC in the treatment group (bosutinib with ketoconazole or rifampin) to the control group (bosutinib alone).