Parameter |
Statistic |
5 mg |
15 mg |
40 mg |
80 mg |
80 mg fed |
120
mg |
|
n/nmiss |
6/0 |
6/0 |
6/0 |
6/0 |
6/0 a
|
5/0 |
AUC0-∞ (nmol∙h/L) |
Mean (SD) |
786 (298) |
2360 (481) |
6280 (1650) |
9180 (1510) |
14800 (5650)
a
|
17300 (4620) |
|
Median
(Min, Max)
|
707
(516, 1280)
|
2150
(1970, 3120)
|
6490
(3660, 7960)
|
9400
(6570, 10900)
|
11700
(11400, 21300)
|
15900
(11900, 22900)
|
|
Geometric mean |
743 |
2330 |
6070 |
9060 |
14200 |
16800 |
|
Geometric CV (%) |
37.2 |
19.4 |
30.2 |
17.9 |
36.5 |
27.5 |
AUC0-t (nmol∙h/L) |
Mean (SD) |
633 (281) |
2160 (412) |
5760 (1500) |
8260 (1230) |
6410 (2330) |
17100
(4680) |
|
Median
(Min, Max)
|
544
(371, 1120)
|
1990
(1790, 2840)
|
5900
(3490, 7350)
|
8460
(6000, 9630)
|
5430
(4700, 11000)
|
15700
(11500, 22700)
|
|
Geometric mean |
588 |
2130 |
5580 |
8170 |
6140 |
16600 |
|
Geometric CV (%) |
43.2 |
18.2 |
29.1 |
16.4 |
31.4 |
28.5 |
AUC0-8h (nmol∙h/L) |
Mean (SD) |
NC |
NC |
NC |
4900 (685) |
6410 (2330) |
NC |
|
Median
(Min, Max)
|
|
|
|
5070
(3580, 5550)
|
5430
(4700, 11000)
|
|
|
Geometric mean |
|
|
|
4850 |
6140 |
|
|
Geometric CV (%) |
|
|
|
15.6 |
31.5 |
|
Cmax (nmol/L) |
Mean (SD) |
73.6 (18.4) |
227
(33.0) |
756 (298) |
936 (224) |
1370 (607) |
1940 (326) |
|
Median
(Min, Max)
|
72.3
(51.6, 104)
|
233
(179, 276)
|
633
(469, 1240)
|
905
(678, 1330)
|
1120
(880, 2530)
|
2050
(1550, 2260)
|
|
Geometric mean |
71.8 |
225 |
712 |
916 |
1280 |
1910 |
|
Geometric CV (%) |
25.0 |
14.9 |
38.3 |
23.2 |
39.2 |
17.5 |
tmax (h) |
Median
(Min, Max)
|
1.0
(0.7, 3.0)
|
2.0
(1.0, 4.0)
|
1.5
(0.7, 3.0)
|
1.0
(0.7, 3.0)
|
3.0
(1.0, 8.0)
|
1.0
(0.7, 1.0)
|
t1/2 (h) |
Mean (SD) |
6.4 (1.9) |
6.6 (0.9) |
6.6 (0.9) |
7.1 (1.0) |
6.7 (1.4) a
|
6.9
(1.2) |
|
Median
(Min, Max)
|
6.3
(4.1, 9.0)
|
6.8
(5.1, 7.6)
|
6.5
(5.6, 7.6)
|
6.7
(6.2, 8.8)
|
6.9
(5.2, 8.1)
|
7.3
(4.9, 7.7)
|
CL/F (L/h) |
Mean (SD) |
25.7 (8.6) |
23.8 (4.3) |
24.9 (8.1) |
32.5 (6.2) |
21.3 (6.6) a
|
26.6
(7.2) |
|
Median
(Min, Max)
|
25.8
(14.2, 35.1)
|
25.4
(17.4, 27.7)
|
22.4
(18.2, 39.7)
|
31.0
(26.5, 44.2)
|
24.8
(13.6, 25.4)
|
27.5
(19.0, 36.6)
|
|
Geometric mean |
24.4 |
23.4 |
23.9 |
32.1 |
20.5 |
25.9 |
|
Geometric CV (%) |
37.2 |
19.4 |
30.2 |
17.9 |
36.5 |
27.5 |
Vz/F (L) |
Mean (SD) |
225 (58.6) |
223 (41.7) |
234 (64.3) |
328 (59.0) |
205.3 (77.6) a
|
260 (56.5) |
|
Median
(Min, Max)
|
230
(159, 316)
|
227
(167, 275)
|
219
(160, 320)
|
304
(276, 430)
|
191
(136, 289)
|
260
(196, 327)
|
|
Geometric mean |
219 |
220 |
226 |
324 |
196 |
256 |
|
Geometric CV (%) |
26.7 |
19.4 |
28.0 |
17.0 |
39.3 |
22.3 |