Table 3.
Exposure metrics comparison of different alternative dosing regimens compared to reference derived from the final POPPK model [mean ± SD]
| Exposure parameters (% relative change) [mean ± SD] | 40 mg QD fasted (reference) | 60 mg QD 2 days + 1 day skip (fasted) | 40 mg QD 2 days + 1 day skip (fed) | 20 mg QD fasted (reference) | 40 mg q72h fed | |
|---|---|---|---|---|---|---|
| Cmin,ss (ng/mL)1 | [529 ± 254] | −11.65% [469 ± 245] | −4.73% [504 ± 258] | [269 ± 127] | −17.84% [221 ± 121] | |
| Cmax,ss (ng/mL) | [727 ± 383] | 5.2% [765 ± 354] | 12.65% [819 ± 365] | [387 ± 201] | 51.68% [587 ± 368] | |
| AUCss,72 h (ng·h/mL)2 | [34270 ± 14700] | 0.02% [34279 ± 15046] | 7.08% [36697 ± 15709] | [17534 ± 7388] | 3.16% [18088 ± 7843] | |
| Cavg,ss (ng/mL)3 | [476] | 0.00% [476] | 6.76% [510] | [244] | 2.87% [251] |
AUC area under the curve, AUCss,72 h area under the concentration–time curve over 72-h dosing interval, Cavg,ss average concentration at steady state, Cmax,ss maximum concentration at steady state, Cmin,ss trough concentration in steady state, POPPK population pharmacokinetic, q72h dosing every 72 h, QD once daily
1The minimum concentration during a 72-h time interval
2The AUC from 864 h to 935 h (72-h time interval)
3Derived by mean of AUCss,72 h/72