TABLE 2

Comparison of pharmacokinetic parameters between two groups of rats treated with CPT-11 (60 mg/kg by i.v. bolus injection) and control vehicle (1% DMSO, v/v) or CPT-11 with 1-day or 5-day thalidomide treatment (100 mg/kg i.p.)

Parameters
Treatment Groups
CPT-11 + Thalidomide
CPT-11 + Control Vehicle
Change
P Value*
Kinetic study with a single-dose of thalidomide
%
C0 (μg/ml) 30.11 ± 19.19 25.23 ± 7.59 19.36 0.543
t1/2β (h) 2.93 ± 0.65 2.59 ± 0.51 13.18 0.293
AUC0-10 h (μg · h/ml) 60.91 ± 11.57 45.97 ± 10.96 32.50 0.029
AUC0-∞ (μg · h/ml) 67.29 ± 14.96 48.40 ± 11.79 39.02 0.022
Vd (l/kg) 3.77 ± 0.27 4.87 ± 1.39 22.51 0.063
CL (l/h/kg) 0.94 ± 0.26 1.34 ± 0.49 -29.68 0.083
SN-38
Cmax (μg/ml) 0.86 ± 0.23 0.92 ± 0.17 -5.91 0.622
t1/2β (h) 4.38 ± 0.64 7.18 ± 1.48 -39.05 0.001
AUC0-10 h (μg · h/ml) 3.31 ± 0.42 4.39 ± 0.70 -24.58 0.005
AUC0-∞ (μg · h/ml) 4.45 ± 0.66 7.75 ± 1.85 -42.62 0.001
SN-38G
Cmax (μg/ml) 2.57 ± 1.15 2.57 ± 0.58 0.04 0.999
t1/2β (h) 4.38 ± 1.72 3.74 ± 1.32 17.01 0.718
AUC0-10 h (μg · h/ml) 6.86 ± 0.95 7.74 ± 0.39 -11.39 0.348
AUC0-∞ (μg · h/ml) 8.54 ± 0.14 8.97 ± 0.27 -4.81 0.180
Kinetic study with 5-day multiple doses of thalidomide
C0 (μg/ml) 14.28 ± 1.25 7.70 ± 0. 27 85.56 0.012
t1/2β (h) 2.13 ± 0.58 1.91 ± 0.13 11.33 0.455
AUC0-10 h (μg · h/ml) 29.60 ± 1.32 20.35 ± 2.23 45.49 0.001
AUC0-∞ (μg · h/ml) 30.28 ± 0.93 20.91 ± 2.35 44.82 0.002
Vd (l/kg) 4.85 ± 1.10 7.95 ± 0.71 -38.98 0.001
CL (L/h/kg) 1.65 ± 0.45 2.90 ± 0.36 -43.03 0.002
SN-38
Cmax (μg/ml) 0.52 ± 0.08 0.70 ± 0.14 -26.36 0.043
t1/2β (h) 5.06 ± 1.50 6.86 ± 1.82 -26.31 0.145
AUC0-10 h (μg · h/ml) 3.43 ± 0.53 4.78 ± 0.66 -28.12 0.011
AUC0-∞ (μg · h/ml) 4.80 ± 0.93 7.68 ± 0.84 -37.53 0.002
SN-38G
Cmax (μg/ml) 2.40 ± 0.75 1.93 ± 0.75 24.56 0.384
t1/2β (h) 2.50 ± 0.18 3.92 ± 2.21 -36.12 0.190
AUC0-10 h (μg · h/ml) 7.38 ± 1.67 5.68 ± 2.43 29.92 0.253
AUC0-∞ (μg · h/ml)
7.90 ± 1.74
6.99 ± 4.04
13.01
0.660

  • ↵* Comparison of the two groups using the Student's unpaired t test