The in Vivo Study of Drug Action: Principles and Applications of Kinetic-Dynamic Modelling

Pharmacodynamics is the oldest in vitro element of pharmacology and the youngest in vivo element. However, over the last decade there has been significant progress in understanding the kinetics of drug action in vivo and pharmacodynamics now ranks with pharmacokinetics in the content of clinical pharmacology journals. The purpose of this book is to link theory and practice of in vivo pharmacodynamic studies. This presents a major challenge due to the multi-faceted nature of the kinetics of drug actions. The first step involves identification of those effects which represent the actions of a drug using mathematical models in combination with classical receptor theory. Subsequently, these effects must be quantified in a precise and reproducible manner and the pharmacokinetcs of the drug and its active metabolites must be accurately described. Finally, realistic models must be developed which identify the site of action and can describe and predict the time course of drug action under physiological and pathological conditions. As in the development of most sciences the theory is in advance of the practice.