IR PF-06650833 dose group | ||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
IR 1 mg | IR 3 mg | IR 10 mg | IR 30 mg | IR 30 mg (Fed) | IR 100 mg | IR 300 mg | IR 1000 mg | IR 2000 mg (fed) | IR 6000 mg (fed) | MR 30 mg | MR 30 mg (fed) | MR 100 mg | MR 300 mg | |
N, na | 8, 8 | 8, 8 | 8, 7 | 15, 14 | 8, 7 | 8, 5 | 8, 6 | 8, 6 | 8, 0 | 8, 6 | 8, 7 | 8, 8 | 8, 7 | 8, 4 |
AUCinf, ng•h/mL | 5.141 (37) | 17.33 (49) | 82.65 (48) | 206.4 (29) | 325.7 (29) | 646.4 (48) | 1477 (71) | 2429 (40) | NC | 10,380 (26) | 262.6 (20) | 292.7 (19) | 838.6 (23) | 2042 (45) |
AUClast, ng•h/mL | 4.920 (38) | 17.01 (49) | 81.91 (44) | 203.7 (29) | 328.3 (27) | 549.4 (38) | 1436 (57) | 2270 (39) | 6346 (26) | 10,200 (25) | 248.8 (17) | 291.6 (19) | 762.2 (20) | 1968 (39) |
Cmax, ng/mL | 1.747 (22) | 5.543 (32) | 22.57 (33) | 57.96 (34) | 53.45 (21) | 108.0 (44) | 171.7 (46) | 308.8 (34) | 650.0 (27) | 847.2 (21) | 15.76 (33) | 41.24 (34) | 42.81 (36) | 64.51 (46) |
Tmax, hb | 1 (0.500–1.00) | 0.525 (0.500–1.00) | 1 (0.500–4.00) | 0.517 (0.500–2.00) | 4.00 (2.00–6.00) | 1 (0.500–2.03) | 2 (0.500–2.00) | 0.75 (0.500–2.00) | 4 (2.00–6.00) | 6 (2.00–6.15) | 6.00 (4.00–12.2) | 6.00 (4.00–8.02) | 8.00 (2.00–16.0) | 4.00 (2.00–12.0) |
t½, hc | 1.86 ± 0.240 | 2.34 ± 0.670 | 3.54 ± 0.139 | 10.2 ± 6.06 | 4.43 ± 1.43 | 15.0 ± 5.22 | 19.9 ± 9.54 | 44.9 ± 69.6 | NC | 72.1 ± 53.9 | 11.7 ± 3.26 | 6.33 ± 1.66 | 9.35 ± 3.62 | 38.8 ± 21.1 |
CL/F, L/h | 194.3 (37) | 173.1 (49) | 121.0 (48) | 145.5 (29) | 92.08 (29) | 154.7 (48) | 203.3 (71) | 411.4 (40) | NC | 577.8 (26) | 114.1 (20) | 102.5 (19) | 119.0 (23) | 147.1 (45) |
Vz/F, L | 516.9 (31) | 567.3 (39) | 617.5 (50) | 1829 (80) | 565.5 (27) | 3189 (51) | 5310 (69) | 14,600 (163) | NC | 49,220 (71) | 1865 (35) | 898.6 (33) | 1476 (31) | 6817 (46) |
Clast, ng/mL | 0.08150 (25) | 0.09984 (69) | 0.1366 (54) | 0.2196 (84) | 0.1651 (98) | 1.218 (147) | 0.9585 (411) | 0.07431 (48) | 0.1599 (348) | 0.08257 (35) | 0.2631 (233) | 0.1490 (91) | 1.881 (345) | 0.1478 (435) |
Tlast, hb | 8.04 (8.00–12.0) | 12 (12.0–24.0) | 24 (24.0–24.0) | 48 (24.0–48.1) | 36.0 (24.0–48.0) | 48 (48.0–48.0) | 96 (96.0–96.0) | 170 (168–363) | 313 (169–313) | 480 (192–481) | 72.0 (48.0–96.0) | 72.0 (48.0–96.0) | 48.0 (48.0–48.0)d | 493 (96.0–528) |
MRT, hc | 3.12 ± 0.525 | 3.40 ± 0.622 | 4.31 ± 0.787 | 6.82 ± 3.38 | 5.43 ± 1.10 | 11.2 ± 4.81 | 20.6 ± 12.6 | 18.7 ± 4.37 | NC | 18.1 ± 6.11 | 17.5 ± 2.35 | 9.27 ± 0.60 | 19.3 ± 5.73 | 50.6 ± 15.9 |