Table 2.
Influence of food on the rate and extent of selumetinib absorption (A) and pharmacokinetic parameters for (B) selumetinib and (C) N-desmethyl-selumetinib in fed and fasted state [all PP population]
| Selumetinib PK parameters | Treatment | n | Geometric LS mean | Pairwise comparision | |
|---|---|---|---|---|---|
| Ratio of fed/fasted | 90% CI | ||||
| (A) | |||||
| AUC (ng*h/mL) | Fed | 21 | 4664 | ||
| Fasted | 19 | 5782 | 0.81 | 0.74, 0.88 | |
| AUC0–t (ng*h/mL) | Fed | 21 | 4504 | ||
| Fasted | 21 | 5639 | 0.80 | 0.73, 0.88 | |
| Cmax (ng/mL) | Fed | 21 | 557 | ||
| Fasted | 21 | 1450 | 0.38 | 0.29, 0.50 | |
| Selumetinib PK parameters | Treatment | n | Geometric mean | CV (%) | |
|---|---|---|---|---|---|
| (B) | |||||
| tmax (h) | Fed | 21 | 4.0a | 1.0, 11.6a | |
| Fasted | 21 | 1.08a | 0.5, 4.0a | ||
| t1/2 (h) | Fed | 21 | 8.6 | 44.5 | |
| Fasted | 19 | 9.4 | 33.0 | ||
| CL/F (L/h) | Fed | 21 | 16.0 | 35.8 | |
| Fasted | 19 | 12.9 | 29.9 | ||
| Vz/F(L) | Fed | 21 | 199.4 | 56.2 | |
| Fasted | 19 | 175.2 | 46.8 | ||
| N-desmethyl-selumetinib PK parameters | Treatment | n | Geometric mean | CV (%) | |
|---|---|---|---|---|---|
| (C) | |||||
| Cmax (ng/mL) | Fed | 21 | 33.5 | 63.8 | |
| Fasted | 21 | 73.9 | 45.7 | ||
| tmax (h)a | Fed | 21 | 4.0a | 1.0, 11.6a | |
| Fasted | 21 | 1.50a | 0.5, 4.0a | ||
| AUC (ng*h/mL) | Fed | 13 | 379.1 | 49.0 | |
| Fasted | 15 | 418.4 | 36.5 | ||
| AUC0–t (ng*/h/mL) | Fed | 21 | 282.4 | 68.2 | |
| Fasted | 21 | 376.4 | 41.0 | ||
| t1/2 (h) | Fed | 13 | 6.8 | 56.6 | |
| Fasted | 15 | 7.7 | 45.5 | ||
aData are presented as median (min, max)