Table 4. Pharmacokinetics of pimasertib.
|
45 mg per day |
60 mg per day |
|||
|---|---|---|---|---|
| Day 1 (test) | Day 8 (reference) | Day 1 (test) | Day 8 (reference) | |
|
Cmax (ng ml−1) | ||||
| N | 9 | 9 | 6 | 6 |
| Median | 145 | 196 | 386 | 332 |
| Range | 82.3–418 | 71.6–660 | 163–516 | 214–638 |
|
Tmax (h) | ||||
| N | 9 | 9 | 6 | 6 |
| Median | 2 | 1.5 | 0.79 | 1.25 |
| Range | 1.00–6.00 | 0.53–2.00 | 0.50–4.00 | 0.50–2.50 |
|
AUC(0–t) (ng ml−1·h) | ||||
| N | 9 | 8 | 5 | 5 |
| Median | 1120 | 1270 | 1390 | 1260 |
| Range | 194–1860 | 190–2030 | 666–2190 | 858–2060 |
|
AUC(0–∞) (ng ml−1·h) | ||||
| N | 7 | 8 | 5 | 5 |
| Median | 1160 | 1340 | 1430 | 1340 |
| Range | 226–1950 | 244–2140 | 673–2310 | 869–2170 |
|
T1/2 (h) | ||||
| N | 7 | 8 | 5 | 5 |
| Median | 5.31 | 5.12 | 5.56 | 5.08 |
| Range | 2.37–5.97 | 3.88–7.27 | 3.53–6.56 | 4.27–6.25 |
|
CL/f (l h−1) | ||||
| N | 7 | 8 | 5 | 5 |
| Median | 38.7 | 34.2 | 42.1 | 44.6 |
| Range | 23.1–199 | 21.0–184 | 25.9–89.1 | 27.6–69.1 |
|
Vz/f (l) | ||||
| N | 7 | 8 | 5 | 5 |
| Median | 276 | 265 | 348 | 395 |
| Range | 197–680 | 189–1030 | 210–570 | 246–425 |
|
Ratio of Cmax test/reference | ||||
| N | 8 | 5 | ||
| Median | 0.837 | 0.751 | ||
| Range | 0.345–1.18 | 0.359–2.22 | ||
|
Ratio of AUC(0–∞) test/reference | ||||
| N | 7 | 4 | ||
| Median | 0.917 | 0.825 | ||
| Range | 0.738–1.22 | 0.759–1.21 | ||
Abbreviations: AUC0–t=area under the concentration–time curve from time zero to the time of last observation; AUC0–∞=area under the concentration–time curve from time zero to infinity; CL/f=apparent oral clearance; Cmax=maximal concentration; FOLFIRI=5-fluorouracil/folinic acid/irinotecan; Tmax=time of maximum concentration; t1/2=apparent half-life; Vz/f=apparent oral volume of distribution.
Pharmacokinetics of pimasertib following single 45 and 60 mg doses on day 1 administered concomitantly with FOLFIRI (test) and following single 45 and 60 mg doses on day 8 administered alone (reference).