Population PKPD Mode.. - Pharsight Corporation
Population PKPD Mode.. - Pharsight Corporation
Population PKPD Mode.. - Pharsight Corporation
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Typical POP PK <strong>Mode</strong>l Development Workflow<br />
Developing the Base PK <strong>Mode</strong>l<br />
Structural <strong>Mode</strong>l<br />
How many compartments<br />
are needed for disposition ?<br />
What input function can<br />
describe the absorption ?<br />
Statistical <strong>Mode</strong>l<br />
Deterministic<br />
Component<br />
⎡θ<br />
⎤<br />
1<br />
Θ=<br />
⎢<br />
θ<br />
⎥<br />
⎢<br />
2 ⎥<br />
⎢θ<br />
⎥<br />
3<br />
⎣<br />
⎦<br />
Disposition function<br />
One-Two-or Three-compartments<br />
Non-linearities, target-mediated…<br />
Input function<br />
What random effects on<br />
parameters are needed or<br />
supported by the data ?<br />
What residual variability<br />
model to use ?<br />
Stochastic<br />
Component<br />
Between subject variability (BSV) matrix<br />
Distributional assumption (Log-normal)<br />
Full Block<br />
Full Diagonal<br />
Reduced<br />
Residual variability model<br />
Additive, proportional, combined<br />
⎡Ω11<br />
Ω=<br />
⎢<br />
⎢<br />
Ω Ω<br />
⎢⎣<br />
0 0<br />
⎡σ<br />
12 22<br />
⎤<br />
11<br />
Σ= ⎢<br />
0 σ ⎥<br />
22<br />
⎣<br />
⎦<br />
⎤<br />
⎥<br />
⎥<br />
Ω ⎥<br />
33 ⎦<br />
slide 29<br />
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