TABLE 4.
Predictive performance of the PK modeld
| Dose regimena | Trial data
|
Simulated data
|
% differencec
|
||||||
|---|---|---|---|---|---|---|---|---|---|
| AUC0-τ,ss (ng·h/ml) | Cmax,ss (ng/ml) | Cmin,ss (ng/ml) | AUC0-τ,ss (ng·h/ml) | Cmax,ss (ng/ml) | Cmin,ss (ng/ml) | AUC0-τ,ss | Cmax,ss | Cmin,ss | |
| 50 mg QD | 5,215.08 (1,068.2) | 423.6 (85.62) | 112.36 (24.95) | 5,347.26 (1,405.9) | 460.94 (115.87) | 114.64 (62.19) | 2.53 | 8.81 | 2.03 |
| 75 mg QD | 7,580.19 (2,188.45) | 642.83 (205.19) | 156.67 (33.96) | 8,020.89 (2,108.85) | 691.41 (173.8) | 171.97 (93.29) | 5.81 | 7.56 | 9.77 |
| 100 mg QD | 9,919.53 (2,628.9) | 780.5 (130.75) | 234.33 (102.32) | 10,694.52 (2,811.8) | 921.88 (231.73) | 229.29 (124.38) | 7.81 | 18.11 | −2.15 |
| 150 mg QD* | 11,785.26 (1,971.95) | 870.4 (129.62) | 278.8 (53.97) | 12,178.91 (3,202.07) | 1,049.84 (263.89) | 261.11 (141.64) | 3.34 | 20.62 | −6.35 |
| 150 mg BID* | 12,260.34 (2,924.38) | 1,488.3 (336.89) | 593.67 (131.31) | 12,041.42 (3,160.33) | 1,716.71 (442.92) | 810.51 (392.65) | −1.79 | 15.35 | 36.53b |
a
*, relative bioavailability was adjusted to 41% in simulation.
b
Evening troughs were used for comparison; if morning troughs were used, the value would be −12.52%.
c
Percent difference was calculated as 100·(simulated data − trial data)/trial data.
d
Values in parentheses indicate the standard deviations. Trial and simulated data are given to two decimal places, different from those in Table 1, which are presented as three significant digits.