Table 3.
Pharmacokinetic parameters of dasatinib, paclitaxel, and 6-OH paclitaxel.
| A. Summary of pharmacokinetic parameters for dasatinib.
| |||
|---|---|---|---|
| Parameters | Treatment | ||
| Dasatinib alone (N=14) | Paclitaxel and dasatinib (N=18) | ||
| Cmax (ng/mL) | Geo Mean (%CV) | 129 (57) | 78 (88) |
| AUC(0-T) (ng•h/mL) | Geo Mean (%CV) | 469 (41) | 415 (63) |
| AUC(TAU) (ng•h/mL) | Geo Mean (%CV) | 478 (43) | 415 (63) |
| Tmax (h) | Median (min, max) | 2.00 (0.50, 6.00) | 2.00 (0.50, 6.00) |
| T-HALF (h) | Mean (SD) | 6.17 (2.32) | 5.27 (1.26) |
| B. Summary of pharmacokinetic parameters for paclitaxel and 6-OH paclitaxel.
| |||||
|---|---|---|---|---|---|
| Parameters | Treatment | ||||
|
| |||||
| Paclitaxel | 6-OH Paclitaxel | ||||
| Paclitaxel alone (N=20) | Paclitaxel and Dasatinib (N=18) | Paclitaxel alone (N=20) | Paclitaxel and Dasatinib (N=18) | ||
| Cmax (ng/mL) | Geo Mean (%CV) | 4824 (37) | 3907 (23) | 349 (44) | 260 (58) |
| AUC(0-T) (ng•h/mL) | Geo Mean (%CV) | 15662 (28) | 13338 (25) | 732 (53) | 562 (68) |
| AUC(INF) (ng•h/mL) | Geo Mean (%CV) | 16088 (28) | 13761 (26) | 771 (53) | 615 (68) |
| T-HALF (h) | Mean (SD) | 11.7 (1.6) | 11.7 (3.8) | 1.26 (0.75) | 0.94 (0.47) |
| MRT(INF) (h) | Mean (SD) | 6.7 (1.5) | 6.9 (2.1) | - | - |
| CLt (L/h) | Mean (SD) | 20.9 (6.3) | 24.3 (6.0) | - | - |
| Vss (L) | Mean (SD) | 140.5 (52.3) | 163.4 (50.4) | - | - |
| M/Pa | Mean (SD) | - | - | 0.06 (0.04) | 0.05 (0.02) |
The parameters are dose-normalized to 100 mg of dasatinib, assuming dose proportionality.
The parameters are dose-normalized to 175 mg/m2, assuming dose proportionality.
Cmax, maximum observed plasma concentration; Tmax, time of maximum observed plasma concentration; AUC(0-T), area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration; AUC(TAU), area under the plasma concentration-time curve within the dosing interval (TAU = 24 h); AUC(INF), area under the plasma concentration-time from time zero to infinity; T-HALF, plasma half-life; MRT(INF), mean residence time adjusted for infusion time (paclitaxel only); CLt, total body clearance (paclitaxel only); Vss, volume of distribution at steady state (paclitaxel only); M/P, metabolite to parent ratio based on dose normalized AUC(INF) (6-OH paclitaxel only).