Table III.
Reduced T-DM1 PK Model Parameter Estimates
| Rat | Cynomolgus monkey | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Parameter | Description | Unit | Value | RSE (%) | llV (%) | RSE (%) | Value | RSE (%) | llV (%) | RSE (%) |
| CLTT | Total trastuzumab clearance | mL/day | 2.37 | (4.9) | 24.6 | (19) | 19.9 | (9.8) | 19.8 | (23) |
| V 1 | Central volume | mL | 10.7 | (4.0) | 19.8 | (12) | 154 | (4.8) | 7.65 | (18) |
| CLd2 | Distributional Clearance 2 | mL/day | 59.7 | (32) | – | – | 56.8 | (46) | – | – |
| V2 | Peripheral volume 2 | mL | 2.52 | (28) | 68.0 | (39) | 50.0 | (60) | – | – |
| CLd3 | Distributional Clearance 3 | mL/day | 13.9 | (11) | – | – | 60.4 | (35) | – | – |
| V 3 | Peripheral volume 3 | mL | 15.5 | (4.9) | 16.5 | (18) | 84.7 | (50) | 27.3 | (43) |
| CLDEC | Deconjugation clearance | mL/day | 2.24 | (3.4) | 15.3 | (18) | 22.0 | (6.9) | 11.9 | (28) |
| CLT-DM1 a | T-DM1 clearance | mL/day | 4.61 | – | – | – | 41.9 | – | – | – |
| TT t 1/2γ b | Total trastuzumab terminal t1/2 | day | 8.84 | – | – | – | 10.5 | – | – | – |
| T-DM1 t 1/2γ b | T-DM1 terminal t1/2 | day | 4.77 | – | – | – | 5.21 | – | – | – |
| Res err | Residual error | % | 10.9 | (5.6) | – | – | 9.64 | (16) | – | – |
T-DM1 trastuzumab emtansine, IIV interindividual variability, RSE relative standard error, t 1/2 half-life, PK pharmacokinetic
aDerived by: CLT-DM1 = CLTT + CLDEC
bDerived by three-compartment PK equation for terminal half-life