Clinically observed and PBPK model–predicted pharmacokinetic parameters of crizotinib in cancer patients following 28-day multiple oral administration of crizotinib 250 mg twice daily
Data are expressed as geometric mean with percent coefficient of variation (CV%) in parentheses (n = 5 for the observed; n = 15 per group × 6 groups for the predicted).
| Crizotinib | Faa | Cmax | AUC0–τ | NSIb |
|---|---|---|---|---|
| ng/ml | ng⋅h/ml | |||
| Observed | − | 328 (25) | 3054 (32) | 1.3 |
| Predicted (on)c | 0.5 | 515 (49) | 6165 (49) | 2.1 |
| P/Od | 1.6 | 2.0 | ||
| Predicted (off)c | 0.5 | 209 (44) | 2500 (44) | − |
| On/Offe | 2.5 | 2.5 | ||
| Predicted (on)c | 0.3 | 266 (52) | 3182 (52) | 1.1 |
| P/Od | 0.81 | 1.2 | ||
| Predicted (off)c | 0.3 | 126 (44) | 1500 (44) | − |
| On/Offe | 2.1 | 2.1 |
−, not applicable.
↵a Crizotinib fraction absorbed used as the simulation input parameter.
↵b An index of nonstationary pharmacokinetics calculated by AUC0–τ at steady state divided by AUC0–∞ for the single-dose results (i.e., 2321 and 2878 ng⋅h/ml for the observed and predicted results, respectively, in Table 3).
↵c The simulation results with (on) and without (off) crizotinib DDI parameters.
↵d Ratio of the predicted to observed results.
↵e Ratio of the predicted results on over off.