Pharmacokinetic and Pharmacodynamic Modelling

When to use

Any question about what the body does to a drug or what the drug does to the body: deriving exposure metrics from concentration-time data, fitting a structural model, building or checking a population analysis, choosing a dose or a regimen, relating exposure to effect, comparing formulations, or scaling to a new population.

The three rules

1. Fix the exposure metric and the analysis population before computing anything. AUC(0-t), AUC(0-inf), AUC(0-tau) at steady state, and Cavg are different quantities and answer different questions. So do AUCinf based on observed versus predicted Clast. Choosing after seeing the numbers is how a negative study becomes positive.

2. Structural model, variability model, and covariate model are three separate decisions. They get conflated constantly — an extra compartment added to absorb what is really unmodelled between-occasion variability, a covariate added to fix what is really a misspecified absorption model. Diagnose which one is wrong before changing any of them.

3. Convergence is not identifiability. A fit that converges with 200% relative standard error on a p…