Table 2.
Mean (±SD) pharmacokinetic variables of temsirolimus and sirolimus
| Temsirolimus |
||||||
|---|---|---|---|---|---|---|
| Dose (mg) | Cmax (μg/mL) | t1/2 (h)* | AUC (μg × h/mL) | CL (L/h) | Vdss (L) | |
| Group A (n = 13) † | 170 | 1.66 (±0.85) | 9.81 (±3.19) | 3.53 (±1.53) | 53.97 (±17.29) | 533 (±265) |
| Group A (n = 6) | 250 | 2.36 (±1.64) | 8.83 (±2.71) | 5.03 (±2.92) | 66.15 (±41.69) | 470 (±362) |
| Group B (n = 13) ‡ | 250 | 1.45 (±0.89) | 9.38 (±2.16) | 3.32 (±0.84) | 79.60 (±18.61) | 699 (±241) |
| Group B (n = 4) | 330 | 2.95 (±1.70) | 10.37 (±3.01) | 3.58 (±0.67) | 94.46 (±16.90) | 654 (±414) |
| Sirolimus |
||||||||
|---|---|---|---|---|---|---|---|---|
|
Cmax (ng/mL) |
Tmax (h) |
t1/2* (h) |
AUC (μg × h/mL) |
Troughs (ng/mL) |
AUC ratio (SIR/TEM) |
AUCsum (μg × h/mL) |
||
| 168 h | C2D1 | |||||||
| Group A † (n = 13) | 185.47 (±87.11) |
3.47 (±3.41) |
38.34 (±56.05) |
10.97 (±5.93) |
15.48 (±8.19), n = 10 |
12.67 (±7.73), n = 3 |
3.56 (±2.29) |
14.49 (±5.74) |
| Group A (n = 6) | 260.60 (±125) |
1.66 (±1.48) |
51.35 (±24.43) |
14.49 (±4.94) |
14.97 (±6.30), n = 4 |
9.55 (±2.29), n = 3 |
3.37 (±1.27) |
19.52 (±6.65) |
| Group B ‡ (n = 13) | 131.83 (±46.37) |
5.01 (±1.94) |
28.86 (±13.55) |
6.83 (±3.28) |
6.82 (±0.38), n = 4 |
– | 2.12 (±0.93) |
9.74 (±3.67) |
| Group B (n = 4) | 246.11 (±1.08) |
1.81 (±1.00) |
23.69 (±4.17) |
7.93 (±2.79) |
13.15 (n = 1) |
9.90 (n = 1) |
2.35 (±1.04) |
11.50 (±2.30) |
Abbreviations: CL, clearance; C2D1 cycle 2, day 1; SIR, sirolimus; TEM, temsirolimus.
*
Harmonic mean.
†
Group A (non-EIAEDs).
‡
Group B (EIAEDs).