Impact of pharmacodynamic variability on drug delivery(1)

Modern pharmaceutical delivery systems are intended to produce plasma drug concentration versus time profiles that result in optimum therapeutic efficacy and a minimum of drug concentration-dependent adverse effects. To accomplish this requires that the drug delivery rate and temporal profile be based on the pharmacokinetic and pharmacodynamic characteristics of the specific medicinal agent. Pharmacokinetic and pharmacodynamic parameters are subject to considerable interindividual variability. Whereas the importance of pharmacokinetic variability is generally recognized, the significance of pharmacodynamic variability (i.e., variability in the relationship between effect intensity and drug concentration) is not as widely appreciated. Pharmacodynamic variability is typically quite large, reproducible, and often substantially exceeds the relative magnitude of pharmacokinetic variability. This article consists of a review of how to assess pharmacodynamic variability, clinical examples of pharmacodynamic variability of drugs with a wide range of indications, and an outline of mechanisms of pharmacodynamic variability.