PK Parameter (unit) | N | n | Route of Administration | Geometric Mean (CVb %) | 95% Confidence Interval |
---|---|---|---|---|---|
Total radioactivity following 10 µg i.v. [14C]nemiralisib + 1000 μg inhaled nemiralisib and 800 μg oral [14C]nemiralisib | |||||
Cmax (pq/ml) | 6 | 6 | i.v. | 204 (52.3) | (122, 343) |
6 | 6 | Oral | 704 (24.4) | (546, 906) | |
tmaxa (h) | 6 | 6 | i.v. | 0.233 (0.233, 0.233) | NA |
6 | 6 | Oral | 7.00 (2.00, 8.02) | NA | |
AUC0–tb (h*pg Eq/ml) | 6 | 6 | i.v. | 770 (17.7) | (641, 926) |
6 | 6 | Oral | 31,730 (35.7) | (22,057, 45,644) | |
AUC0–inf (h*pg Eq/ml) | 6 | 3 | i.v. | 813 (8.18) | (664, 996) |
6 | 1 | Oral | 34,749 (NE) | NE | |
t1/2 (h) | 6 | 3 | i.v. | 56.9 (7.70) | (47.0, 68.9) |
6 | 1 | Oral | 39.6 (NE) | NE | |
Ae urinec (total radioactivity ng Eq) | 6 | 6 | i.v. | 1044 (NA) | NA |
CLr (l/h) (total radioactivity) | 6 | 6 | i.v. | 1.25 (16.8) | (1.05, 1.49) |
Intravenous [14C]nemiralisib | |||||
Radiometric dose (µg) | 6 | 6 | i.v. | 8.10 (3.2) | (7.83, 8.37) |
Cmax (pg/ml) | 6 | 6 | i.v. | 206 (57.9) | (117, 362) |
tmaxa (h) | 6 | 6 | i.v. | 0.233 (0.233, 0.233) | NA |
AUC0–td (h*pg/ml) | 6 | 6 | i.v. | 546 (45.3) | (347, 860) |
AUC0–inf (h*pg/ml) | 6 | 4 | i.v. | 751 (48.3) | (362, 1555) |
AUC0–t ratio | 6 | 6 | i.v. | 0.709 (29.2) | (0.525, 0.958) |
AUC0–inf ratio | 6 | 2 | i.v. | 0.722 (50.3) | (0.010, 51.406) |
t1/2 (h) | 6 | 4 | i.v. | 54.7 (36.0) | (31.4, 95.4) |
CLe (l/h) | 6 | 4 | i.v. | 10.8 (46.7) | (5.32, 21.9) |
Vz (l) | 6 | 4 | i.v. | 851 (14.0) | (682, 1062) |
Vss (l) | 6 | 4 | i.v. | 728 (11.2) | (609, 870) |
Inhaled nemiralisib | |||||
Nominal dose (µg) | 6 | 6 | Inhaled | 1000 (0) | NA |
Cmax (pg/ml) | 6 | 6 | Inhaled | 5259 (62.8) | (2871, 9633) |
tmaxa (h) | 6 | 6 | Inhaled | 0.0333 (0.017, 0.050) | NA |
AUC0–tf (h*pg/ml) | 6 | 6 | Inhaled | 28,426 (34.5) | (19,998, 40,406) |
AUC0–inf (h*pg/ml) | 6 | 6 | Inhaled | 33,374 (33.2) | (23,773, 46,854) |
t1/2 (h) | 6 | 6 | Inhaled | 58.4 (16.8) | (49.0, 69.7) |
Oral nemiralisib | |||||
Radiometric dose (µg) | 6 | 6 | Oral | 769 (0.65) | (763, 774) |
Cmax (pg/ml) | 6 | 6 | Oral | 399 (27.8) | (300, 531) |
tmaxa (h) | 6 | 6 | Oral | 6.00 (2.00, 8.00) | NA |
AUC0–tg (h*pg/ml) | 6 | 6 | Oral | 16,913 (53.8) | (9960, 28,719) |
AUC0–inf (h*pg/ml) | 6 | 4 | Oral | 25,108 (46.3) | (12,451, 50,632) |
AUC0–t ratio | 6 | 6 | Oral | 0.533 (24.7) | (0.413, 0.688) |
AUC0–inf ratio | 6 | 1 | Oral | 0.377 (NE) | NE |
t1/2 (h) | 6 | 4 | Oral | 50.8 (40.2) | (27.5, 94.0) |
CLr (l/h) (parent nemiralisib) | 6 | 6 | Oral | 0.93 (from pooled radioprofiling) | NE |
N, number of subjects; n, number of evaluable subjects; NA, not applicable; NE, not estimable; Vz, volume of distribution during terminal phase after intravenous administration.Vss, volume of distribution at steady state
↵a tmax expressed as median and range.
↵b AUC0–t = 168 h for intravenous and 96–168 h for oral.
↵c Ae urine, total radioactivity in urine sample (0–168 h) shown as arithmetic mean.
↵d AUC0–t = 72–168 h.
↵e 10.8 l/h based on plasma or (10.8 l/h/1.08 ratio) 10.0 l/h for blood, i.e., corrected for blood:plasma ratio of 1.08 (unpublished GSK data).
↵f AUC0–t = 96–168 h.
↵g AUC0–t = 72–168 h.