In Vivo Pharmacology

The ultimate therapeutic value of a molecule is determined by its effect in vivo; factors such as plasma protein binding, endogenous physiological tone and reflexes can obscure the relationship between free drug concentration and observed effect. This chapter centers on the various pharmacokinetic and pharmacodynamic factors involved in the production of in vivo drug response. The response to a drug may be observed directly or through a surrogate such as a biochemical biomarker. In addition, there may be temporal dissociation between the actual biochemical events initiated by the drug and the eventual lasting therapeutic response. Since in vivo systems are open systems, response must be linked with the time of exposure to the drug. Specifically, the kinetics of drug movement within the body are immensely important to the in vivo activity of drugs either through restricted diffusion to and from the compartments containing the therapeutic target or through the actual rate of dissociation of the drug from the target itself. Since the body is an open system (not in equilibrium), the kinetics of interaction of drugs with targets becomes paramount and a major determinant of overall in vivo activity.