Table 4.
Mean (SD) pharmacokinetic parameters of trabectedin and dFdU in patients coadministered single doses of trabectedin and gemcitabine
| Parameter | Trabectedin
|
dFdU
|
||||
|---|---|---|---|---|---|---|
| Dose level 1 (n = 6) | Dose level 2 (n = 3) | Dose level 3 (n = 6) | Dose level 1 (n = 6) | Dose level 2 (n = 3) | Dose level 3 (n = 6) | |
| tmax (h)a | 1.99 (0.5–3.00) | 2.80 (2.00–2.83) | 2.01 (2.00–2.80) | NA | 0.98 (0.28–1.03) | 0.97 (0.33–1.07) |
| Cmax (ng/mL)b | 1.96 (1.14) | 1.79 (0.375) | 3.35 (1.44) | NA | 17.0 (10.4) | 38.7 (4.4) |
| AUC∞ (ng h/mL)c | 13 (15.3) | 9.82 (1.46) | 15.8 (6.61) | NA | 119 (67.9) | 225 (33.5) |
| t½ (h)d | 35.8 (51.9) | 43.4 (36.1) | 32.7 (14.1) | NA | 6.82 (0.278) | 4.79 (0.829) |
| CL (L/h) | 73.0 (45.3) | 79.6 (4.0) | 49.9 (19.4) | NA | NR | NR |
| Vss (L) | 722 (591) | 2527 (2774) | 1089 (770) | NA | NR | NR |
AUC area under the plasma concentration–time curve, Cmax maximum plasma concentration, CL systemic clearance, dFdU 2′-deoxy-2′,2′-difluorouridine, NA not applicable, NR not reported, SD standard deviation, tmax time to Cmax, t1/2 terminal half-life, Vss apparent volume of distribution at steady state
a
Median (range)
b
For dFdU, μg/mL
c
For dFdU, μg h/mL
d
For dFdU, t1/2λ(h)