Table 1.
Escalating single and multiple dosages of bumped kinase inhibitors administered orally to determine maximum tolerated doses and toxicity profiles.
| BKI – |
Determined maximum tolerated single oral dose (mg/kg) |
Multiple PO dose concentrations used mg/kg of body weight (dose frequency) |
Observed signs of toxicity – |
Plasma concentration at 2 h post last dose Avg ± S.D. (μM) |
|---|---|---|---|---|
| 1369 | 600 | 500 (QD) | After 3rd dose | 11.5 ±1.5 |
| 300 (QD) | After 5th dose | 8.3 ± 0.2 | ||
| 150 (QD) | None after 7th dose | 3.9 ± 1.5 | ||
| 1534 | 250a | 250 (QD) | After 4th dose | 2.9 ± 1.5 |
| 100 (QD) | After 5th dose | 1.8 ± 0.9 | ||
| 1649 | 100 | 50 (QD) | After 5th dose | 307 ± 26.8 |
| 30 (QoD) | None after 5th dose | 46.8 ±1.7 | ||
| 10 (QoD) | None after 5th dose | 17.9 ±1.0 |
QD, once per day; QoD, every other day; Avg, average.
a
No signs of toxicity observed after a single dose, however the BKI reached its solubility limit in vehicle and no higher concentration could be tested.