Pharmacokinetics, pharmacodynamics and drug disposition

During the last decade, the application of pharmacokinetic and pharmacodynamic modeling techniques has become an increasingly important aspect of contemporary clinical psy-chopharmacology (1–5). These techniques have been ap-plied during the process of development of new drug entities as well as for the improved understanding of the clinical actions of drugs that are already marketed. Techniques for the study of drug metabolism in vitro have advanced sub-stantially during the last decade, and now are an integral component of preclinical drug development and the link to subsequent clinical studies of drug metabolism and dispo-sition. Kinetic-dynamic modeling techniques have been combined with in vitro metabolism procedures and in vi-tro–in vivo mathematical scaling models to provide insight into the general problem of pharmacokinetic drug interac-tions in clinical psychopharmacology (6–9). This chapter reviews some advances in pharmacokinetics, pharmacodynamics, and drug metabolism, along with methodologic applications to selected problems in clinical psychopharmacology. POPULATION PHARMACOKINETICS Principles Pharmacokinetic studies based on a traditional intensive-design model are usually conducted using carefully selected volunteer subjects, a controlled experimental design, and collection of multiple blood samples. After measurement of drug and metabolite concentrations in all samples, pharma