Table 2.
Non-compartmental pharmacokinetic parameters of the three formulations of galunisertib.
| Parametersa | Galunisertib (150 mg) | ||
|---|---|---|---|
| HSWG (N=14) | RCD (N=14) | RCS (N=14) | |
| tmaxb (h) | 1.00 (0.50–3.08) | 2.00 (0.50–3.17) | 2.00 (0.50–3.00) |
| Cmax (μg/L) | 954 (89.7) | 734 (68.0) | 769 (67.8) |
| AUC(0–12) (μg·h/L) | 3,430 (64.6) | 3,170 (56.1) | 2,970 (63.0) |
| AUC(0–24) (μg·h/L) | 4,070 (61.5) | 3,840 (53.7) | 3,660 (64.3) |
| AUC(0-tlast) (μg·h/L) | 4,520 (58.5) | 4,360 (52.0) | 4,350 (63.9) |
| AUC(0–48) (μg·h/L) | 4,520 (58.6) | 4,360 (52.0) | 4,340 (63.8) |
| AUC(0-∞) (μg·h/L) | 4,740 (55.6) | 4,490c (53.3) | 4,790d (70.9) |
| CL/F (L/hr) | 31.7 (55.6) | 33.4c (53.3) | 31.3d (70.9) |
| Vz/F (L) | 505 (88.0) | 473c (76.0) | 511d (81.9) |
| t1/2 (h) | 11.1 (47.0) | 9.81c (41.1) | 11.3d (42.4) |
All pharmacokinetic parameters except tmax evaluated after a single dose on Day 1 of each period are geometric mean (% CV) (unless stated otherwise).
tmax is median (range);
N=12;
N=11. AUC(0-∞), CL/F, Vz/F, and t1/2 not reported for patients where extrapolated AUCtlast-inf>20%.
Abbreviations: AUC = area under the plasma concentration versus time curve; AUC(0-∞) = AUC from zero to infinity; AUC(0-tlast) = AUC from time zero to time t where t is the last time point with a measurable concentration; AUC(0-x) = AUC from time zero to time x where x is the last time point with a measurable concentration; CL/F = clearance; Cmax = maximum plasma drug concentration; CV = coefficient of variation; HSWG = high-sheer wet granulation; N = number of subjects used in pharmacokinetic analysis; RCD = roller compaction dry-milled; RCS = roller compaction slurry-milled; t1/2 = half-life associated with the terminal rate constant in non-compartmental analysis; tmax = time of maximum plasma drug concentration; Vz/F = volume of distribution.