Table 3.
Preliminary mean (%CV) dacomitinib plasma pharmacokinetic parameters following single (D-9) and multiple dosing (C1D14)
| Single dose (D-9) | ||||||||
|---|---|---|---|---|---|---|---|---|
| QD dose (mg) | N | Tamax (h) | Cmax (ng/mL) | AUC24 (h.ng/mL) | AUCinf (h.ng/mL) | t1/2 (h) | CL/F(L/h) | *Rbss |
| 15 | 3 | 24 (6.0–24.0) | 8.0 (31) | 9.48 (39) | 660.3 (25) | 61.1 (25) | 23.7 (26) | 1.12 (0.95–1.31) |
| 30 | 3 | 8 (8.0–24.0) | 12.2 (55) | 6.52 (51) | 987.5 (33) | 98.0 (45) | 32.0 (34) | 1.39 (1.18–1.62) |
| 45 | 7 | 6 (4.0–24.0) | 21.2 (71) | 7.98 (58) | 1,604 (31) | 80.0 (15) | 30.4 (32) | 1.21 (1.10–1.33) |
| Multiple dose (C1D14) | ||||||||
| QD dose (mg) | N | Tamax (h) | Cmax (ng/mL) | Cctrough (ng/mL) | Cave (ng/mL) | AUCτ (h.ng/mL) | CL/F(L/h) | *Rdac |
| 15 | 2e | 15 (6.0–24.0) | 32.0 (11) | 28.2–33.2 | 29.7 (17) | 713 (17) | 21.4 (17) | 6.32 (4.73–8.45) |
| 30 | 3 | 4 (0.0–8.0) | 64.3 (19) | 49.0–56.5 | 56.3 (22) | 1,353 (21) | 22.9 (22) | 7.37 (2.82–19.28) |
| 45 | 6 | 8 (4.0–8.0) | 81.2 (21) | 60.9–76.6 | 75.1 (23) | 1,803 (20) | 26.1 (23) | 6.37 (4.91–8.27) |
AUC inf area under the concentration–time curve from time zero to infinity; AUC τ AUC over the dosing interval at steady state; C max maximum plasma concentration; C avemean plasma concentration at steady state; C trough trough plasma concentration; CL/F clearance; R ac accumulation ratio; R sslinearity ratio; t 1/2 terminal half-life; T max time to Cmax; %CV percentage coefficient of variation; QD once daily
aMedian (min, max); b AUCτ/AUCinf; c range (min, max) of averaged Ctrough concentrations from Day 1 of Cycles 2 to 4; d AUCτ/AUC24; e for n = 2, parameters are presented as mean (min, max); * geometric mean ratio and 90% confidence interval