Hybrid (bolus-infusion) flavopiridol PK
| Dose level . | Bolus-infusion, mg/m2 . | No. of patients . | Total/unbound . | Day 1 end of bolus, μM . | Day 1 end of infusion, μM . | Pretreatment day 2, μM . | Pretreatment day 3, μM . | Day 1 AUC last, μM/hr . |
|---|---|---|---|---|---|---|---|---|
| 1 | 20/30 | 5 | Total | 0.84 ± 0.09 | 0.56 ± 0.16 | 0.05* | 0.11* | 4.1 ± 2.3 |
| Unbound | 0.075 ± 0.020 | 0.053 ± 0.030 | 0.005* | 0.009* | 0.38 ± 0.26 | |||
| 2 | 25/35 | 9 | Total | 1.51 ± 0.41 | 0.71 ± 0.33 | 0.05 ± 0.03 | 0.04 ± 0.01 | 8.9 ± 5.1 |
| Unbound | 0.126 ± 0.026 | 0.086 ± 0.033 | 0.005 ± 0.003 | 0.005 ± 0.001 | 1.06 ± 0.61 | |||
| 3 | 30/40 | 6 | Total | 0.93 ± 0.16 | 0.59 ± 0.19 | 0.02, 0.03* | BLQ | 5.4 ± 2.4 |
| Unbound | 0.120 ± 0.051 | 0.069 ± 0.024 | 0.003, 0.003* | BLQ | 0.62 ± 0.24 | |||
| 4 | 30/50 | 4 | Total | 1.06 ± 0.31 | 0.79 ± 0.32 | 0.03, 0.06* | 0.04, 0.06* | 7.3 ± 3.5 |
| Unbound | 0.123 ± 0.065 | 0.079 ± 0.026 | 0.004, 0.007* | 0.005, 0.006* | 0.76 ± 0.34 | |||
| 5 | 30/60 | 20 | Total | 1.57 ± 0.46 | 1.48 ± 0.60 | 0.04 ± 0.02 | 0.07 ± 0.05 | 16.8 ± 8.3 |
| Unbound | 0.168 ± 0.056 | 0.141 ± 0.051 | 0.005 ± 0.002 | 0.009 ± 0.009 | 1.67 ± 0.82 | |||
| 6 | 30/70 | 2 | Total | 0.12, 1.08 | 1.45, 1.52 | 0.08, 1.45 | 0.04, N.S. | 19.4, 30.9 |
| Unbound | 0.012, 0.131 | 0.138, 0.155 | 0.007, 0.197 | 0.006, N.S. | 1.92, 3.60 |
| Dose level . | Bolus-infusion, mg/m2 . | No. of patients . | Total/unbound . | Day 1 end of bolus, μM . | Day 1 end of infusion, μM . | Pretreatment day 2, μM . | Pretreatment day 3, μM . | Day 1 AUC last, μM/hr . |
|---|---|---|---|---|---|---|---|---|
| 1 | 20/30 | 5 | Total | 0.84 ± 0.09 | 0.56 ± 0.16 | 0.05* | 0.11* | 4.1 ± 2.3 |
| Unbound | 0.075 ± 0.020 | 0.053 ± 0.030 | 0.005* | 0.009* | 0.38 ± 0.26 | |||
| 2 | 25/35 | 9 | Total | 1.51 ± 0.41 | 0.71 ± 0.33 | 0.05 ± 0.03 | 0.04 ± 0.01 | 8.9 ± 5.1 |
| Unbound | 0.126 ± 0.026 | 0.086 ± 0.033 | 0.005 ± 0.003 | 0.005 ± 0.001 | 1.06 ± 0.61 | |||
| 3 | 30/40 | 6 | Total | 0.93 ± 0.16 | 0.59 ± 0.19 | 0.02, 0.03* | BLQ | 5.4 ± 2.4 |
| Unbound | 0.120 ± 0.051 | 0.069 ± 0.024 | 0.003, 0.003* | BLQ | 0.62 ± 0.24 | |||
| 4 | 30/50 | 4 | Total | 1.06 ± 0.31 | 0.79 ± 0.32 | 0.03, 0.06* | 0.04, 0.06* | 7.3 ± 3.5 |
| Unbound | 0.123 ± 0.065 | 0.079 ± 0.026 | 0.004, 0.007* | 0.005, 0.006* | 0.76 ± 0.34 | |||
| 5 | 30/60 | 20 | Total | 1.57 ± 0.46 | 1.48 ± 0.60 | 0.04 ± 0.02 | 0.07 ± 0.05 | 16.8 ± 8.3 |
| Unbound | 0.168 ± 0.056 | 0.141 ± 0.051 | 0.005 ± 0.002 | 0.009 ± 0.009 | 1.67 ± 0.82 | |||
| 6 | 30/70 | 2 | Total | 0.12, 1.08 | 1.45, 1.52 | 0.08, 1.45 | 0.04, N.S. | 19.4, 30.9 |
| Unbound | 0.012, 0.131 | 0.138, 0.155 | 0.007, 0.197 | 0.006, N.S. | 1.92, 3.60 |
Data are mean ± SD. If n = 2, individual values are reported.
AUC indicates area under the curve.
Remaining samples were below limits of quantitation.