Table 3.
Pharmacokinetic Parameters of α-FLT3-scFv and α-FLT3-A192 nanoparticles following IV administration using a two-compartment model
| Parameter (Unit) | α-FLT3 scFva (n=5) | α-FLT3-A192a (n=5) | p value |
|---|---|---|---|
| dose of total protein (nmol) | 20.6 (1.7) | 31.1 (5.7) | 0.004 |
| dose of rhodamine (nmol) | 5.52 (0.45) | 50.9 (9.4) | <0.0001 |
| Body weight (g) | 25.0 (2.0) | 18.8 (3.5) | 0.009 |
| A (μM) | 5.45 (1.80) | 31.6 (43.7) | 0.21 |
| B (μM) | 2.30 (1.37) | 1.83 (1.27) | 0.59 |
| α (h−1) | 12.1 (18.9) | 4.56 (1.63) | 0.40 |
| β (h−1) | 0.44 (0.19) | 0.056 (0.030) | 0.002 |
| t1/2α (h) | 0.26 (0.21) | 0.17 (0.05) | 0.36 |
| t1/2β (h) | 2.34 (2.20) | 14.7 (5.6) | 0.002 |
| C0 (μM) | 7.75 (2.31) | 33.4 (44.9) | 0.24 |
| AUC (μmol*h) | 6.73 (2.05) | 38.8 (14.6) | 0.001 |
| CL/g BW (ml/h·g) | 0.04 (0.01) | 0.08 (0.02) | 0.009 |
| V1/g BW (ml/g) | 0.03 (0.01) | 0.17 (0.09) | 0.008 |
| kelimination (h−1) | 1.17 (0.27) | 0.69 (0.62) | 0.15 |
| kplasma→tissue (h−1) | 5.18 (8.19) | 3.47 (1.52) | 0.66 |
| ktissue→plasma (h−1) | 6.18 (10.9) | 0.46 (0.28) | 0.27 |
a
values indicate the mean (standard deviation) of n=5 following a dose of 2.7 nanomoles of rhodamine-labeled α-FLT3-A192 (1.7 nanomoles of the total dose per gram BW of α-FLT3-A192) per gram of mouse body weight or a dose of 0.2 nanomoles of rhodamine-labeled α-FLT3 scFv (0.8 nanomoles per gram BW of the total dose of α-FLT3 scFv) alone. The average mouse body weight across these studies is 22 g.