PK parameters of TMZ in plasma and tumor IF in SF188V+ tumor-bearing athymic rats receiving multiple i.v. administrations of TMZ at a dose level of either 18 mg/kg (CD regimen) or 3.24 mg/kg (MD regimen)
Values are means ± S.D.
Parameters | CD (n = 7) | MD (n = 9) | ||||
|---|---|---|---|---|---|---|
| Day 1 | Day 5 | Day 1 | Day 28 | |||
| Plasma | ||||||
| Cmax'p (μg/ml) | 24.1 ± 3.7 | 21.6 ± 3.2 | 3.17 ± 0.26 | 3.33 ± 0.54 | ||
| AUCo→∞,p (μg·h/ml) | 24.1 ± 2.6 | 25.0 ± 5.7 | 4.27 ± 1.45 | 3.72 ± 0.89 | ||
| Vp (l/kg) | 0.91 ± 0.30 | 0.98 ± 0.44 | 1.14 ± 0.18 | 1.18 ± 0.41 | ||
| CLp (l/h/kg) | 0.73 ± 0.11 | 0.75 ± 0.15 | 0.85 ± 0.22 | 0.92 ± 0.21 | ||
| Ke (h-1) | 0.87 ± 0.26 | 0.86 ± 0.29 | 0.75 ± 0.16 | 0.81 ± 0.12 | ||
| t1/2 (h) | 0.85 ± 0.20 | 0.89 ± 0.28 | 0.97 ± 0.27 | 0.87 ± 0.13 | ||
| Tumor IF | ||||||
| Cmax,t (μg/ml) | 10.6 ± 3.6 | 11.1 ± 5.9 | 4.85 ± 4.08 | 2.03 ± 0.58 | ||
| tmax,t (h) | 0.51 ± 0.21 | 0.77 ± 0.22 | 0.44 ± 0.23 | 0.45 ± 0.34 | ||
| AUCo→∞,t (μg·h/ml) | 21.0 ± 5.4 | 31.7 ± 15.1 | 6.59 ± 4.16 | 4.55 ± 2.56 | ||
| Vt (ml) | 1.22 ± 0.30 | 1.33 ± 0.32 | 1.13 ± 0.20 | 1.41 ± 0.61 | ||
| AUCo→∞ ratio | ||||||
| AUCtumor/AUCplasma | 0.90 ± 0.35 | 1.22 ± 0.49 | 1.56 ± 1.01 | 1.31 ± 0.84 | ||
| Intercompartmental rate constant | ||||||
| Kpt (h-1) | 4.30 ± 5.00 | 2.69 ± 1.30 | 6.68 ± 7.50 | 6.77 ± 3.21* | ||
| Ktp (h-1) | 3.02 ± 2.28 | 1.88 ± 1.47 | 5.01 ± 3.96 | 5.13 ± 5.07 | ||
↵* P < 0.01 comparing with the CD group on day 5 using the Wilcoxon rank-sum test.