Pharmacokinetic summary of AG014699
| Cohort | 699 dose | Temozolomide dose | Cmax (ng/mL) | AUC0-24 (ng h/mL) | AUCinf* (ng h/mL) | Vd (L) | Cl* (L/h) | t1/2 (h) | |
|---|---|---|---|---|---|---|---|---|---|
| Mean (CV%) | Mean (CV%) | Mean (CV%) | Mean (CV%) | Mean (CV%) | Mean (CV%) | ||||
| 1 | 1 mg/m2 (n = 3) | 100 | day -7 | 25 (23) | 21 (34) | 24 (39) | 111† (34) | 73† (28) | 1.2† (55) |
| day 1 | 27 (7) | 33 (74) | 38 (70) | 160† (78) | 54† (55) | 3.3† (119) | |||
| day 4 | 27 (27) | 44 (93) | — (—) | 400† (113) | 57† (55) | 11.6† (155) | |||
| 2 | 2 mg/m2 (n = 3) | 100 | day -7 | 72 (21) | 137 (53) | 171 (80) | 218 (51) | 35 (42) | 6.9 (121) |
| day 1 | 85 (15) | 100 (23) | 107 (14) | 217 (50) | 40 (3) | 3.8 (17) | |||
| day 4 | 74 (16) | 156 (40) | — (—) | 317 (71) | 30 (38) | 8.0 (88) | |||
| 3 | 4 mg/m2 (n = 3) | 100 | day -7 | 169 (61) | 228 (18) | 350 (42) | 584 (101) | 23 (32) | 23.2 (123) |
| day 1 | 134 (17) | 205 (31) | 254 (41) | 401 (50) | 32 (43) | 10.6 (69) | |||
| day 4 | 159 (18) | 278 (24) | — (—) | 403 (41) | 27 (21) | 10.9 (51) | |||
| 4 | 8 mg/m2 (n = 4) | 100 | day -7 | 456 (24) | 877 (38) | 1,384 (70) | 281 (33) | 16 (66) | 19.9 (88) |
| day 1 | 473 (33) | 877 (28) | 1,107 (25) | 299 (33) | 15 (23) | 13.9 (16) | |||
| day 4 | 559 (54) | 1,335 (39) | — (—) | 324 (26) | 13 (38) | 18.3 (30) | |||
| 5-8 | 12 mg/m2 (n = 12) | 100-200 | day -7 | 675 (71) | 861 (35) | 1,021 (35) | 423 (50) | 25 (32) | 11.5 (37) |
| day 1 | 551 (73) | 893 (35) | 1,178 (47) | 423 (44) | 24 (39) | 15.0 (80) | |||
| day 4 | 531 (37) | 1,480 (59) | — (—) | 505 (56) | 21 (49) | 16.8 (41) | |||
| 9 | 18 mg/m2 (n = 6) | 200 | day -7 | 700 (61) | 1,550 (66) | 1,952 (62) | 410 (41) | 23 (47) | 13.1 (40) |
| day 1 | 837 (58) | 1,923 (74) | 2,721 (82) | 378 (49) | 19 (57) | 16.0 (46) | |||
| day 4 | 863 (41) | 2,882 (82) | — (—) | 343 (39) | 18 (50) | 15.2 (37) |