PF-06650833 dose group | |||||||
---|---|---|---|---|---|---|---|
IR 25 mg BID | IR 100 mg BID | IR 250 mg BID | IR 750 mg BID | IR 1000 mg QIDa | IR 330 mg TID | MR 300 mg QD | |
Day 1 | |||||||
N | 8 | 8 | 8 | 8 | 8 | 8 | 8 |
AUCtau, ng•h/mL | 163.7 (26) | 566.3 (32) | 1348 (40) | 2581 (28) | 2008 (25) | 1500 (38) | 1150 (62) |
Cmax, ng/mL | 29.96 (34) | 101.8 (38) | 226.4 (35) | 470.3 (24) | 517.3 (30) | 309.0 (37) | 149.3 (51) |
Tmax, hb | 2.03 (1.00–4.00) | 2.03 (1.00–4.00) | 4.00 (2.00–4.00) | 3.12 (2.03–4.07) | 4.00 (2.00–4.02) | 2.03 (2.00–4.00) | 4.00 (2.00–10.0) |
Day 14 | |||||||
N | 8 | 8 | 8 | 7 | – | 8 | 7 |
AUCtau, ng•h/mL | 204.2 (26) | 776.5 (16) | 1360 (39) | 2475 (24) | – | 1599 (28) | 975.4 (65) |
Cmax, ng/mL | 36.19 (31) | 127.6 (16) | 238.5 (33) | 420.7 (25) | – | 317.9 (27) | 146.8 (49) |
Tmax, hb | 2.00 (0.500–4.00) | 2.02 (1.00–4.00) | 2.02 (2.00–4.03) | 2.00 (2.00–4.00) | – | 2.00 (1.00–4.00) | 4.00 (2.00–7.50) |
CL/F, L/h | 122.4 (26) | 128.9 (16) | 183.7 (39) | 302.9 (24) | – | 206.1 (28) | 308.0 (65) |
Vz/F, L | 9650 (37) | 8064 (27) | 10,170 (44) | 13,160 (29) | – | 10,070 (24) | 11,600 (46) |
Cmin, ng/mL | 4.064 (46) | 14.13 (40) | 20.07 (76) | 33.07 (50) | – | 51.48 (68) | 6.471 (55) |
Cav, ng/mL | 17.03 (26) | 64.72 (16) | 113.3 (39) | 206.3 (24) | – | 200.1 (28) | 40.62 (65) |
PTF | 1.868 (21) | 1.740 (16) | 1.911 (14) | 1.868 (12) | – | 1.307 (18) | 3.383 (37) |
Rac | 1.250 (19) | 1.373 (23) | 1.009 (13) | 0.9377 (32) | – | 1.068 (26) | 0.8985 (24) |
Rac, Cmax | 1.209 (22) | 1.253 (28) | 1.052 (22) | 0.8689 (38) | – | 1.029 (28) | 1.078 (29) |
t½, hc | NR | NR | NR | 29.4d ± 1.78 | – | 31.4e ± 5.60 | 25.4f ± 6.41 |
MRT, h | NR | NR | NR | 6.15d ± 0.366 | – | 5.29e ± 1.18 | 20.3f ± 9.46 |
Ae24% | 0.7288 (27) | 0.9414 (29) | 0.4822 (53) | 0.4885 (24) | – | 0.6372 (34) | 0.300 (70) |
CLr, mL/min | 13.62 (19) | 18.54 (19) | 13.92 (18) | 23.14 (19) | – | 18.83 (21) | 15.39 (30) |