6 Exposure- Response Modeling: Methods and Practical Implementation
reducing QT prolongation may be much lower than estimated from a model
assuming an instantaneous exposure effect. Appropriate assessment of the ef-
fect requires developing a dynamic model descr ibing the temporal rela tionship
between the pharmacokinetics (PK) time pro file and the QT time profile. This
type of model and related analytical methods will be described in Chapter 6.
1.2.2 Theophylline
This example comes from a study to find the optimal conc entration of theo-
phylline for the manage ment of acute airway obstruc tion. This is an early
study using a randomized concentration controlled (RCC) design (Holford et
al., 199 3a, 1993b). In the study, 174 patients were randomized