Table 3.

Pharmacokinetic summary of AG014699

Cohort699 doseTemozolomide doseCmax (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%)
11 mg/m2 (n = 3)100day -725 (23)21 (34)24 (39)111 (34)73 (28)1.2 (55)
day 127 (7)33 (74)38 (70)160 (78)54 (55)3.3 (119)
day 427 (27)44 (93)— (—)400 (113)57 (55)11.6 (155)
22 mg/m2 (n = 3)100day -772 (21)137 (53)171 (80)218 (51)35 (42)6.9 (121)
day 185 (15)100 (23)107 (14)217 (50)40 (3)3.8 (17)
day 474 (16)156 (40)— (—)317 (71)30 (38)8.0 (88)
34 mg/m2 (n = 3)100day -7169 (61)228 (18)350 (42)584 (101)23 (32)23.2 (123)
day 1134 (17)205 (31)254 (41)401 (50)32 (43)10.6 (69)
day 4159 (18)278 (24)— (—)403 (41)27 (21)10.9 (51)
48 mg/m2 (n = 4)100day -7456 (24)877 (38)1,384 (70)281 (33)16 (66)19.9 (88)
day 1473 (33)877 (28)1,107 (25)299 (33)15 (23)13.9 (16)
day 4559 (54)1,335 (39)— (—)324 (26)13 (38)18.3 (30)
5-812 mg/m2 (n = 12)100-200day -7675 (71)861 (35)1,021 (35)423 (50)25 (32)11.5 (37)
day 1551 (73)893 (35)1,178 (47)423 (44)24 (39)15.0 (80)
day 4531 (37)1,480 (59)— (—)505 (56)21 (49)16.8 (41)
918 mg/m2 (n = 6)200day -7700 (61)1,550 (66)1,952 (62)410 (41)23 (47)13.1 (40)
day 1837 (58)1,923 (74)2,721 (82)378 (49)19 (57)16.0 (46)
day 4863 (41)2,882 (82)— (—)343 (39)18 (50)15.2 (37)
  • * AUC0-inf and Cl may not be reflected accurately as the extrapolation for AUC0-inf was >20% of the AUC0-24 for some patients.

  • Not included in statistical analysis. This value may not be correctly estimated due to insufficient data.