Using Population Pharmacokinetic and Pharmacodynamic Modeling to Guide Dosing in Drug Development when the “Average Patient” Does Not Exist.


When discussing optimal dosing, the implicit assumption is often made that there is a single “optimal” dosing regimen that is appropriate for all patients. This may be the case in some circumstances – for example, if the therapeutic concentration window is wide, and if pharmacokinetic and pharmacodynamic variability among subjects is not too great. This presentation will consider scenarios which mitigate against a common dosing regimen being suitable for all subjects. In particular, the following situations will be discussed:

* relatively narrow target concentration window 
* high inter-subject variability in pharmacodynamic behavior, leading to a target concentration window that differs across subjects
* high inter-subject variability in pharmacokinetic behavior, necessitating consideration of different dosing regimens for different subjects

The way in which each of these situations can complicate choice of a suitable dosing regimen will be illustrated in the context of a Phase II study of a IIbIIIa inhibitor in subjects following an acute coronary event.

David Giltinan, Ph.D.
Staff Scientist (Biostatistics)
Genentech, Inc.