3 µg | 10 µg | 30 µg | 100 µg | 300 µg | 600 µg | 1200 µg | 1.25 mg oral solution | 200 µg inhaled, with activated charcoal | 200 µg inhaled, without activated charcoal | 50 µg 1-h intravenous solution | |
SRD trial | |||||||||||
Subjects | 5# | 6 | 6 | 6 | 6 | 6 | 6 | ||||
Cmax pmol·L−1 | 17.8 (32.9) | 50.1 (46.6) | 129 (40.1) | 462 (53.2) | 1090 (26.0) | 3130 (30.6) | 6500 (73.1) | ||||
tmax h | 0.083 (0.033–0.083) | 0.083 (0.083–0.167) | 0.100 (0.083–0.167) | 0.134 (0.083–0.183) | 0.167 (0.167–0.183) | 0.167 (0.083–0.167) | 0.183 (0.167–0.250) | ||||
AUC0–1 pmol·L−1·h | 10.4 (42.4) | 28.7 (49.0) | 73.7 (43.4) | 299 (45.2) | 706 (25.9) | 1700 (34.5) | 3920 (76.4) | ||||
AUC0–∞ pmol·L−1·h | 23.8 (88.2) | 85.7 (55.3) | 208 (37.1) | 959 (45.0) | 2370 (23.1) | 5820 (38.9) | 13500 (65.3) | ||||
CL/F mL·min−1 | 3700 (88.2) | 3430 (55.3) | 4230 (37.1) | 3070 (45.0) | 3730 (23.1) | 3030 (38.9) | 2610 (65.3) | ||||
t1/2 h | 1.24 (76.2) | 2.43 (28.5) | 2.70 (35.7) | 4.23 (40.2) | 6.04 (50.0) | 10.2 (23.2) | 15.5 (15.2) | ||||
MRD trial | |||||||||||
Subjects | 8 | 8 | 8 | 8¶ | 8 | ||||||
Day 1 | |||||||||||
Cmax pmol·L−1 | 55.2 (36.1) | 158 (27.4) | 391 (24.4) | 1330 (43.5) | 4000 (28.0) | ||||||
AUC0–12 pmol·L−1·h | 82.5 (24.5) | 226 (23.2) | 734 (22.5) | 2430 (35.2) | 6320 (21.3) | ||||||
tmax h | 0.083 (0.033–0.167) | 0.083 (0.083–0.167) | 0.167 (0.083–0.250) | 0.167 (0.083–0.250) | 0.150 (0.133–0.233) | ||||||
t1/2 h | 2.04 (29.3) | 2.44 (16.1) | 3.26 (23.2) | 7.17 (15.8) | 7.43 (19.6) | ||||||
fe0–12 % | 0.721 (37.1) | 0.664 (49.5) | 0.696 (66.2) | 0.766 (65.4) | 0.831 (39.8) | ||||||
Day 8 | |||||||||||
Cmax,ss pmol·L−1 | 55.6 (25.7) | 143 (38.5) | 640 (42.7) | 1710 (35.5) | 3670 (39.9) | ||||||
tmax,ss h | 0.083 (0.083–0.167) | 0.083 (0.083–0.200) | 0.125 (0.083–0.250) | 0.167 (0.083–0.250) | 0.159 (0.117–0.233) | ||||||
AUCτss pmol·L−1·h | 104 (18.8) | 284 (40.0) | 1190 (29.4) | 3800 (29.3) | 7010 (36.4) | ||||||
fe0–12ss % | 1.06 (25.0) | 1.14 (32.8) | 1.38 (45.3) | 1.36 (54.6) | 0.874 (72.9) | ||||||
RACmax | 1.01 (32.9) | 0.905 (39.8) | 1.64 (32.0) | 1.35 (31.7) | 0.917 (26.9) | ||||||
RAAUC0–12 | 1.26 (22.5) | 1.25 (28.1) | 1.62 (24.5) | 1.60 (28.1) | 1.11 (32.0) | ||||||
Bioavailability | |||||||||||
Subjects | 12 | 12 | 12 | 12 | |||||||
Cmax pmol·L−1 | 62.5 (49.4) | 1910 (25.7) | 1800 (31.0) | 2040 (17.1) | |||||||
tmax h | 0.750 (0.500–1.000) | 0.167 (0.083–0.250) | 0.167 (0.167–0.250) | 0.742 (0.500–0.983) | |||||||
AUC0–∞ pmol·L−1·h AUC0–∞ pmol·L−1·h | 277 (62.1) | 3590 (25.5) | 3590 (20.8) | 2230 (15.3) | |||||||
F % | 0.50 (37.8) | 40.5 (20.8) | 40.2 (16.8) | N/A |
Data are presented as n, geometric mean (geometric coefficient of variance) or median (range), unless otherwise stated. SRD: single-rising-dose; Cmax: maximum measured concentration of BI 1265162 in plasma after single dose; tmax: time administered drug excreted from last dosing to the maximum concentration of BI 1265162 in plasma after single dose; AUC0–1: area under the curve of BI 1265162 in plasma from dosing to 1 h post-dosing; AUC0–∞: area under the concentration–time curve of BI 1265162 in plasma over the time interval from 0 extrapolated to infinity; CL/F: apparent clearance; t1/2: observed terminal elimination half-life of BI 1265162 in plasma; MRD: multiple-rising-dose; AUC0–12: area under the curve of BI 1265162 in plasma over a 12-h period after single dose; fe0–12: fraction of administered drug excreted unchanged in urine over a 12-h period after single dose; Cmax,ss: maximum measured concentration of BI 1265162 in plasma at steady state; tmax,ss: time administered drug excreted from last dosing to the maximum concentration of BI 1265162 in plasma at steady state; AUCτ,ss: area under the curve of BI 1265162 in plasma over a 12-h period at steady state; fe0–12,ss: fraction of administered drug excreted unchanged in urine over a 12-h period at steady state; RACmax: accumulation ratio based on Cmax,ss; RAAUC: accumulation ratio based on AUC0–12 and AUCτ,ss; F: absolute bioavailability; N/A: not applicable. #: n=6 for Cmax and tmax; ¶: n=7 on day 8.