
6
Modeling dynamic exposure–response
relationships
Until now we have a ssumed that the e ffect of e xposure on the response is
instantaneous. However, this assumption is rarely true, although so metimes
reasonable as an approximation. In pharmacometrics, in most cases, the PD
change lags behind the PK change that caused it, a phenomenon known as
hysteresis. In this case, it is importa nt to investigate and to mo de l the tem-
poral relationship between PK a nd PD. Ignoring hysteresis may induce bias
in the estimation of exposure–response relationships. Even when hysteresis
does not cause significant bias, if not dealt with prope rly, it may increase the ...