Table 3.
Model Estimated Parameters for Pharmacodynamic Analysis. Parameters are Reported as Mean and Standard Error (SE, %)
| Parameter (Unit) | Definition | Estimate | SE (%) |
|---|---|---|---|
| DOX MW (g/mol) | Molecular weight | 543.5 | - |
| ABE MW (g/mol) | Molecular weight | 602.7 | - |
| DOX fu | The fraction of drug unbound to protein | 0.25 | - |
| ABE fu | The fraction of drug unbound to protein | 0.037 | - |
| F | The oral bioavailability of ABE | 0.45 | - |
| EmaxDOX | Maximum drug-induced effect | 1 | fixed |
| EC50DOX (µM) | The concentration of drug allowing 50% of Emax | 0.509 | 38.9 |
| EmaxABE | Maximum drug-induced effect | 20 | fixed |
| EC50ABE (µM) | The concentration of drug allowing 50% of Emax | 12.7 | 30.6 |
| τ (h) | Transit time between compartments | 20 | fixed |
| kginvitro (mass⋅h−1) | The first-order rate constant for in vitro cell growth | 0.026 | 4.08 |
| ktrans(h−1) | The first-order rate constant for cell death and transit between replication and stasis | 0.075 | 16.7 |
| SmaxCDK | Maximum effect from inhibition of CDK | 4.21 | 15.3 |
| kgclin (mass⋅day−1) | The first-order rate constant for clinical cell growth | 0.016 | fixed |
Abbreviations: ABE, abemaciclib; DOX, doxorubicin.