Table 4.
Pharmacokinetic parameters of PEP02 at each dose level
| Dose level (mg/m2) |
C
max
(ug /mL) CPT-11(ng /mL) SN-38 |
T
max
(hr) |
AUC0–169.5
(hr-ug/mL) CPT-11 (hr-ng/mL)SN-38 |
AUC0–∞
(hr-ug/mL) CPT-11 (hr-ng/mL)SN-38 |
V
ss
(L/m2) |
Cl (L/hr/m2) |
t
1/2
(hr) |
MRT0–∞
(hr) |
|
|---|---|---|---|---|---|---|---|---|---|
| Total CPT-11 | 60, N = 1 | 31.8 | 1.5 | 222 | 223 | 3.56 | 0.269 | 28.7 | 13.2 |
| 120, N = 6 | 79.4 ± 13.9 | 2.5 ± 1.1 | 2,835 ± 1,817 | 2,963 ± 1,947 | 1.8 ± 0.771 | 0.0591 ± 0.0367 | 29.5 ± 17.2 | 38.6 ± 19.5 | |
| 180, N = 4 | 102 ± 17.6 | 1.75 ± 0.5 | 1,945 ± 1,029 | 1,963 ± 1,035 | 1.97 ± 0.342 | 0.119 ± 0.0703 | 22.3 ± 11.5 | 20.5 ± 9.47 | |
| SN-38 | 60, N = 1 | 2.58 | 3.6 | 38.4 | NC | NA | NA | NC | NC |
| 120, N = 6 | 9.20 ± 3.50 | 21.9 ± 26.3 | 710 ± 395 | 997 ± 680 | NA | NA | 75.4 ± 43.8 | 109.0 ± 54.4 | |
| 180, N = 4 | 14.3 ± 6.16 | 21.0 ± 9.0 | 1,159 ± 969 | 1,425 ± 1,134 | NA | NA | 58.0 ± 32.8 | 90.9 ± 43.1 |
Mean ± SD; C max peak concentration in plasma; T max time to achieve peak plasma concentration; AUC 0–169.5, AUC 0–∞ area under the plasma concentration–time curve from time zero to 169.5 h and infinity, respectively; V ss volume of distribution at steady state; t 1/2 plasma terminal elimination half-life; Cl total clearance of drug from plasma; MRT 0–∞ mean residence time from time zero to infinity; NC not calculated because there was no distinct terminal log-linear phase for the λ z determination; NA not available