Table 6.
Summary of the primary PK parameters of BEZ235
| Timepoint/dose level/statistics | AUClast (ng h/mL) | AUCinf (ng h/mL) | AUC0 − 24 (ng h/mL) | Cmax (ng/mL) | Tmax (h) |
|---|---|---|---|---|---|
| Cycle 1 Day 1 | |||||
| 400 mg qd | |||||
| n | 3 | 2 | 3 | 3 | 3 |
| Median | 1036 | 978 | 1038 | 135 | 4.0 |
| Min/Max | 821/13,782 | 895/1061 | 821/13,869 | 69.9/1000 | 4.0/4.0 |
| 800 mg qd | |||||
| n | 3 | 1 | 3 | 3 | 3 |
| Median | 2558 | 1488 | 2558 | 154 | 8.0 |
| Min/Max | 1433/6096 | 1488/1488 | 1438/6096 | 150/466 | 4.0/8.0 |
| 1000 mg qd | |||||
| n | 6 | 3 | 4 | 6 | 6 |
| Median | 4492 | 1407 | 4334 | 472 | 5.0 |
| Min/Max | 869/19,292 | 890/7301 | 869/19,265 | 106/970 | 1.0/8.0 |
| 1200 mg qd | |||||
| n | 5 | 1 | 3 | 5 | 5 |
| Median | 6420 | 2292 | 6417 | 403 | 6.0 |
| Min/Max | 2261/25,472 | 2292/2292 | 2264/15,775 | 203/1500 | 4.0/23.4 |
| 1400 mg qd | |||||
| n | 5 | 1 | 2 | 5 | 5 |
| Median | 10,224 | 1286 | 13,736 | 733 | 8.0 |
| Min/Max | 1208/37,073 | 1286/1286 | 1215/26,258 | 87.7/1940 | 4.0/24.0 |
| 400 mg bid | |||||
| n | 7 | 2 | 4 | 7 | 7 |
| Median | 2283 | 1995 | 1755 | 301 | 6.0 |
| Min/Max | 606/7719 | 1402/2587 | 606/5450 | 84.6/1150 | 1.0/8.0 |
| Cycle 1 Day 8 | |||||
| 400 mg qd | |||||
| n | 3 | 2 | 3 | 3 | 3 |
| Median | 7349 | 14,315 | 7351 | 754 | 4.0 |
| Min/Max | 4311/17,295 | 7657/20,974 | 4310/17,465 | 314/1470 | 4.0/8.0 |
| 800 mg qd | |||||
| n | 3 | 1 | 3 | 3 | 3 |
| Median | 17,327 | 19,866 | 17,327 | 1170 | 6.0 |
| Min/Max | 8497/19,617 | 19,866/19,866 | 8497/19,626 | 609/1700 | 4.0/8.0 |
| 1000 mg qd | |||||
| n | 7 | 3 | 3 | 7 | 7 |
| Median | 9347 | 8301 | 8261 | 912 | 6.0 |
| Min/Max | 482/46,393 | 496/9469 | 482/9347 | 76.1/2850 | 1.0/8.0 |
| 1200 mg qd | |||||
| n | 4 | 1 | 4 | 4 | 4 |
| Median | 33,484 | 14,438 | 34,179 | 1810 | 4.0 |
| Min/Max | 12,760/46,522 | 14,438/14,438 | 12,840/46,522 | 1130/2410 | 2.0/4.0 |
| 1400 mg qd | |||||
| n | 5 | 0 | 3 | 5 | 5 |
| Median | 35,882 | – | 36,375 | 2480 | 4.0 |
| Min/Max | 13,688/74,490 | – | 26,544/40,807 | 720/3910 | 3.9/7.9 |
| 400 mg bid | |||||
| n | 6 | 1 | 5 | 6 | 6 |
| Median | 9702 | 2786 | 10,677 | 1046 | 4.0 |
| Min/Max | 2616/52,196 | 2786/2786 | 2616/53,881 | 455/6070 | 2.0/12.0 |
| Cycle 1 Day 28 | |||||
| 400 mg qd | |||||
| n | 3 | 3 | 3 | 3 | 3 |
| Median | 8916 | 10,192 | 8916 | 795 | 4.0 |
| Min/Max | 7756/25,942 | 7947/29,223 | 7769/26,182 | 600/1860 | 4.0/4.0 |
| 800 mg qd | |||||
| n | 3 | 2 | 3 | 3 | 3 |
| Median | 24,870 | 13,540 | 24,955 | 1980 | 2.0 |
| Min/Max | 417/26,167 | 428/26,651 | 417/26,167 | 41.2/2190 | 1.0/4.0 |
| 1000 mg qd | |||||
| n | 4 | 2 | 2 | 4 | 4 |
| Median | 4804 | 3769 | 3736 | 548 | 4.0 |
| Min/Max | 641/11,714 | 649/6889 | 641/6831 | 153/935 | 1.0/6.0 |
| 1200 mg qd | |||||
| n | 2 | 0 | 1 | 2 | 2 |
| Median | 37,128 | – | 43,429 | 2170 | 5.9 |
| Min/Max | 31,005/43,252 | – | 43,429/43,429 | 1720/2620 | 3.9/8.0 |
| 1400 mg qd | |||||
| n | 4 | 3 | 4 | 4 | 4 |
| Median | 18,270 | 30,688 | 18,343 | 1506 | 4.0 |
| Min/Max | 4394/36,862 | 7815/45,815 | 4394/36,862 | 317/2510 | 4.0/6.0 |
| 400 mg bid | |||||
| n | 4 | 1 | 3 | 4 | 4 |
| Median | 34,083 | 2663 | 29,372 | 3650 | 4.0 |
| Min/Max | 2493/80,497 | 2663/2663 | 2493/40,839 | 518/8290 | 1.0/6.0 |
AUC area under the curve, bid twice daily, Cmax maximum observed serum concentration after drug administration, PK pharmacokinetic, Tmax time to reach Cmax, qd once daily