Integrated pharmacokinetic-dynamic modeling of drugs acting on the CNS.

This paper has attempted to review some of the possibilities we have today to describe the relationships between the kinetics of a drug and the pharmacodynamic responses. In the future we should place a great deal of effort not only on a detailed evaluation of drug absorption and disposition in the body but also on a much more careful characterization of the dose (concentration)-effect relationships. This should be done in vivo, in order to be able to evaluate the complex character of an observed pharmacological effect, and in a dose range as wide as possible. Although not discussed in the present communication, the possibility of active metabolites must always be considered.