Table 3 Plasma pharmacokinetics of single and multiple dosing of dalpiciclib
50 mg QD | 75 mg QD | 100 mg QD | 125 mg QD | 150 mg QD | 175 mg QD | |
|---|---|---|---|---|---|---|
Single dosing | n = 3 | n = 3 | n = 10 | n = 10 | n = 10 | n = 3 |
Tmax, h | 3.0 (2.0–4.0) | 3.0 (3.0–3.0) | 2.5 (2.0–4.0) | 3.5 (2.0–6.0) | 3.5 (2.0–4.0) | 4.0 (3.0–4.0) |
Cmax, ng/mL | 12.2 (57.3) | 20.3 (37.3) | 46.8 (27.5) | 46.6 (56.8) | 63.6 (64.4) | 114 (37.8) |
AUC0-t, h*ng/mL | 482 (40) | 572 (13) | 1170 (20) | 1480 (38) | 1880 (57) | 3080 (24) |
t1/2z, h | 51.0 (13.6) | 46.9 (8.0) | 49.7 (16.6) | 43.7 (23.5) | 51.4 (23.2) | 40.3 (22.4) |
CL/F, L/h | 89.8 (39.2) | 117 (15.7) | 76.1 (20.7) | 76.6 (37.8) | 70.5 (51.9) | 52.8 (21.8) |
Vz/F, L | 6610 (40) | 7900 (12) | 5450 (25) | 4830 (45) | 5230 (71) | 3080 (39) |
Multiple dosing | n = 3 | n = 3 | n = 9 | n = 9 | n = 9 | n = 3 |
Tmax, h | 4.0 (4.0–6.0) | 3.0 (3.0–4.0) | 3.0 (2.0–6.0) | 4.0 (2.0–6.0) | 4.0 (2.0–8.0) | 3.0 (3.0–3.0) |
Cmax, ng/mL | 41.1 (23.9) | 53.4 (9.4) | 87.0 (48.5) | 115 (28.7) | 126 (30.0) | 155 (57.8) |
AUCss, h*ng/mL | 615 (27) | 792 (18) | 1410 (53) | 2020 (32) | 2230 (24) | 2730 (48) |
t1/2z, h | 46.9 (11.9) | 52.3 (6.3) | 48.2 (20.3) | 44.9 (21.2) | 44.9 (17.5) | 45.1 (6.6) |
CLss/F, L/h | 81.4 (26.9) | 94.7 (18.0) | 71.0 (52.5) | 62.0 (31.8) | 67.2 (23.9) | 64.1 (47.8) |
Vz/F, L | 5510 (35) | 6920 (31) | 4930 (67) | 4010 (30) | 4350 (32) | 4170 (48) |
Racc(AUC) | 3.4 (41.3) | 3.0 (22.1) | 2.7 (35.9) | 3.3 (60.0) | 2.7 (52.8) | 1.9 (37.7) |