b.Comparison of *10/*10 subjects vs. other extensive metabolizer (EM) subjects for AUC, Cmax, t1/2 and CL/F
| Parameters | Dose | Geometric mean* 10/* 10(n = 7) | Geometric mean,other EMs(n = 9) | Ratio (90% CI) | P-value |
|---|---|---|---|---|---|
| AUC0–∞ (h ng−1 ml−1) | 40 mg single | 4962 | 2242 | 2.21 (1.53, 3.21) | 0.002 |
| Cmax (ng ml−1) | 530 | 360 | 1.47 (1.15, 1.88) | 0.014 | |
| CL/F (l h−1 kg−1) | 0.13 | 0.29 | 0.45 (0.31, 0.65) | 0.002 | |
| t1/2 (h) | 5.44 | 3.36 | 1.62 (1.34, 1.96) | 0.001 | |
| AUCt,ss (h ng−1 ml−1) | 80 mg multiple | 9693 | 4427 | 2.19 (1.53, 3.13) | 0.002 |
| Cmax,ss (ng ml−1) | 1199 | 815 | 1.47 (1.13, 1.92) | 0.023 | |
| SDED/F (l h−1 kg−1) | 0.13 | 0.29 | 0.45 (0.32, 0.65) | 0.002 | |
| t1/2 (h) | 5.17 | 3.74 | 1.38 (1.08, 1.76) | 0.034 |
*
Median (range).
†
Geomean (range).
Cmax and Cmax,ss, Maximum serum concentration; Cav,ss, average steady-state concentration; tmax and tmax,ss, time to maximum serum concentration; AUC0–∞and AUCτ,ss, areas under the serum concentration–time curves, from the time of dosing extrapolated to infinity and during one dosing interval at steady state, respectively; CL/F and CLss/F, apparent clearance; t1/2, terminal half-life; LI, linearity index defined as the ratio of dose-normalized AUCτ,ss/AUC0–∞,day1; RA, accumulation ratio of dose-normalized AUCτ,ss/ AUCτ,day1.)